AQP3在不同年龄段正常人皮肤组织及角质形成细胞、成纤维细胞中的表达
摘要
衰老是指机体器官对环境改变的适应性随年龄增长而逐渐下降,进而易患疾病或引起死亡的一种现象。衰老一方面受机体预定的基因程序调控,另一方面由内外“磨损和消耗”所引起,二者同时表现于细胞和分子水平。皮肤由于位于体表,其衰老主要分为自然衰老和光老化两种形式,其分子机制非常复杂,特别是对皮肤自然衰老机制的研究并不深入。皮肤自然衰老机制代表性的学说有:基因调控学说、自由基学说、代谢失调学说。而遗传基因改变是皮肤内源性衰老的根本。
皮肤自然衰老临床表现的一大特点就是皮肤干燥、脱屑、脆性增加,修复功能减退;组织学上则表现为皮肤变薄,表皮更新减慢,角质层屏障功能下降,以及角质层水合能力下降。正常角质层含水量保持在10%-20%之间,使皮肤柔软,不发生干燥、皲裂现象,但老年人皮肤含水量仅是正常的75%,所以表现为皮肤干燥。同时皮肤组织细胞的水分减少,细胞皱缩、老化、使皮肤出现细小皱纹,酶的活性降低。因此,皮肤的衰老与皮肤含水量、角质层的水合能力及屏障功能有关。
水通道蛋白(AQP)是上世纪90年代发现的一类能快速转运水的膜整合蛋白。目前发现AQP在哺乳动物中有13个亚型,不同AQP亚型的分布具有组织、细胞、亚细胞特异性。根据这些水通道蛋白转运功能特性的差异,将其分为两个亚家族:水选择通道亚家族(aquaporins),这类通道对水分子的通透性具有高度选择性;另一个亚家族是水-甘油通道(aquaglyceroporins),这类通道除对水分子通透外,还对甘油和尿素等中性小分子也具有通透性。皮肤上主要分布的水通道蛋白是AQP3,它属于水-甘油通道蛋白亚家族。目前发现AQP3参与多种生理、病理过程,它与尿液的浓缩、气道表面的液体平衡、肠道水的吸收均有密切关系。而在皮肤的病理生理过程中,AQP3同样可以转运水、甘油到达表皮,因此对于表皮的屏障作用、水的保存有很大的意义。有研究者发现,哺乳动物皮肤AQP3的缺失可导致皮肤干燥,角质层水合作用下降,皮肤弹性下降,以及皮肤屏障修复延迟,生物合成功能受损,伤口愈合延迟。这些便提示我们AQP3参与皮肤衰老的过程。
为了验证AQP3与皮肤衰老的关系,我们首先运用RT-PCR及Western blot研究不同年龄组非曝光部位皮肤组织中AQP3 mRNA、蛋白的表达量。结果显示:1.青年组AQP3 mRNA表达水平为0.654±0.104,中年组AQP3 mRNA表达水平为0.685±0.143,老年组AQP3 mRNA表达水平为0.316±0.109;2.青年组AQP3蛋白表达水平为1.936±0.250,中年组1.813±0.224,老年组1.044±0.271。我们发现老年组皮肤中AQP3 mRNA、蛋白的表达量较青年组和中年组均显著性减少(P值均＜0.01)。
第二部分,我们利用消化分离的方法原代培养了正常人非曝光部位皮肤角质形成细胞和成纤维细胞,进行了细胞鉴定后分别检测了两种细胞不同年龄段AQP3的表达,结果显示:1.角质形成细胞中,青年组AQP3 mRNA表达水平为1.240±0.205,中年组AQP3 mRNA表达水平为0.889±0.136,老年组AQP3 mRNA表达水平为0.392±0.083。AQP3mRNA表达随年龄增加而减少。角质形成细胞中AQP3蛋白表达水平为:青年组1.303±0.231,中年组0.980±0.164,老年组0.360±0.142,AQP3蛋白表达亦随年龄增加而减少。2.成纤维细胞中,青年组AQP3mRNA表达水平为0.881±0.118,中年组AQP3 mRNA表达水平为0.757±0.167,老年组AQP3 mRNA表达水平为0.285±0.143。免疫细胞化学示AQP3蛋白表达水平为:青年组:0.378±0.123,中年组:0.355±0.112,老年组:0.171±0.060。WB示成纤维细胞中AQP3蛋白表达水平为:青年组0.792±0.092,中年组0.692±0.155,老年组0.375±0.112。老年组成纤维细胞AQP3 mRNA、蛋白的表达量较青年组和中年组均显著性减少(P值均＜0.01)。3.青年组角质形成细胞AQP3mRNA、蛋白表达明显高于青年组成纤维细胞(P值均＜0.01),中年组角质形成细胞AQP3蛋白表达明显高于中年组成纤维细胞(P＜0.05),老年组角质形成细胞AQP3 mRNA、蛋白表达与老年组成纤维细胞无显著性差异。
综上所述:AQP3在皮肤组织及体外原代培养的角质形成细胞、成纤维细胞中的表达与年龄有关。AQP3的表达下降与皮肤自然衰老有关。
Aging means that organs' adaptability decreases accompanied with years of age, and human is liable to diseases or death. Aging is regulated by presumptive genes, as well as exterior and interior's abrasions and consume, which are both shown in cell and molecular level. Skin is located in body surface, skin aging comprise natural aging and photoaging. Mechanism of natural aging is not clear, the representative theory include gene regulation theory、free radical theory、metabolic disorder theory. Gene regulation is fundamental of skin natural aging.
One of feature of the clinical manifestation of skin natural aging is xerosis cutis、desquamating、fragility increasing, and recovery hypofunction; the histological manifestation include skin thinning、epidermal renewal stepping down、stratum corneum's barrier and hydration function descending. The normal water content of stratum corneum retained between 10%-20%, which make skin soft; but in old man, the water content of skin is 75% compared normal content, which cause xerosis cutis. Meanwhile,water content of skin cells decrease, which cause tiny shrinkage and enzymatic active decrease. Thus, skin aging is concerned with water content、stratum corneum's barrier and hydration function.
AQP is a kind of membrane integral protein which can fast transport water. AQP has 13 hypotype in mammalian, which are distributed in different tissue and cell. According to the different function of AQPs, AQPs are divided into two subfamily: aquaporins and aquaglyceroporins. The former transport only water; aquaglyceroporins transport not only water but also glycerol. AQP3 is a aquaglyceroporin which is located in skin. AQP3 participate in several patho-physiological functions including urine concentration、water balance of air tube surface、intestinal tract's water absorption. In dermal patho-physiological course, AQP3 can transport water and glycerol to epiderm, so AQP3 is significant to epidermal barrier and water retention. Researchers found AQP3-/- mouse display xerosis cutis、stratum corneum's barrier function descending、skin elasticity descending、skin barrier repairing delayed、and biosynthesis damage、wound healing delay. All of these hint that AQP3 participate skin aging.
In order to identify the relationship between AQP3 and skin aging, we detect the expression of AQP3 mRNA and protein of different ages by RT-PCR and Western blot. The result display: 1 .AQP3 mRNA in teenage group: 0.654±0.104, in middle-age group: 0.685±0.143,in old- age: 0.316±0.109. 2.The expression of AQP3 protein in in teenage group: 1.936 +0.250, in middle-age group: 1.813±0.224,in old- age: 1.044 + 0.271. We found AQP3 mRNA and protein in old-age group significantly lower than the level of middle-age group (P<0.01), and teenage group(P＜0.01)
In the second part, normal human epidermal keratinocytes and skin fibroblast of different ages were cultured; the expression of AQP3 was investigated in keratinocytes and fibroblast respectively. The result display: 1 .in keratinocytes, AQP3 mRNA in teenage group: 1.240±0.205, in middle-age group: 0.889±0.136,in old- age: 0.392±0.083. The expression of AQP3 protein in in teenage group: 1.303±0.231, in middle-age group: 0.980±0.164,in old- age: 0.360 + 0.142. AQP3mRNA and protein in old-age group keratinocytes decreased with the increase of age. 2. In fibroblast, AQP3 mRNA in teenage group: 0.881±0.118, in middle-age group: 0.757±0.167,in old- age: 0.285±0.143. The expression of AQP3 protein by WB in teenage group: 0.792±0.092, in middle-age group: 0.692±0.155,in old- age: 0.375 + 0.112. AQP3 mRNA and protein in old-age group fibroblast decreased significantly (P<0.01). 3. AQP3 mRNA and protein in keratinocytes of teenage group is signify-cantly higher than fibroblasts of teenage group(P＜0.01). AQP3 protein in keratinocytes of middle-age group is significantly higher than fibroblasts of middle-age group(P<0.05). AQP3 mRNA and protein of old-age group in keratinocytes and fibroblasts is not significantly different.
ALL findings suggest the expression level of AQP3 in the human skin is associated with age, and decreases as the age grow. AQP3 may play a important role in aging of human skin.
皮肤自然衰老临床表现的一大特点就是皮肤干燥、脱屑、脆性增加,修复功能减退;组织学上则表现为皮肤变薄,表皮更新减慢,角质层屏障功能下降,以及角质层水合能力下降。正常角质层含水量保持在10%-20%之间,使皮肤柔软,不发生干燥、皲裂现象,但老年人皮肤含水量仅是正常的75%,所以表现为皮肤干燥。同时皮肤组织细胞的水分减少,细胞皱缩、老化、使皮肤出现细小皱纹,酶的活性降低。因此,皮肤的衰老与皮肤含水量、角质层的水合能力及屏障功能有关。
水通道蛋白(AQP)是上世纪90年代发现的一类能快速转运水的膜整合蛋白。目前发现AQP在哺乳动物中有13个亚型,不同AQP亚型的分布具有组织、细胞、亚细胞特异性。根据这些水通道蛋白转运功能特性的差异,将其分为两个亚家族:水选择通道亚家族(aquaporins),这类通道对水分子的通透性具有高度选择性;另一个亚家族是水-甘油通道(aquaglyceroporins),这类通道除对水分子通透外,还对甘油和尿素等中性小分子也具有通透性。皮肤上主要分布的水通道蛋白是AQP3,它属于水-甘油通道蛋白亚家族。目前发现AQP3参与多种生理、病理过程,它与尿液的浓缩、气道表面的液体平衡、肠道水的吸收均有密切关系。而在皮肤的病理生理过程中,AQP3同样可以转运水、甘油到达表皮,因此对于表皮的屏障作用、水的保存有很大的意义。有研究者发现,哺乳动物皮肤AQP3的缺失可导致皮肤干燥,角质层水合作用下降,皮肤弹性下降,以及皮肤屏障修复延迟,生物合成功能受损,伤口愈合延迟。这些便提示我们AQP3参与皮肤衰老的过程。
为了验证AQP3与皮肤衰老的关系,我们首先运用RT-PCR及Western blot研究不同年龄组非曝光部位皮肤组织中AQP3 mRNA、蛋白的表达量。结果显示:1.青年组AQP3 mRNA表达水平为0.654±0.104,中年组AQP3 mRNA表达水平为0.685±0.143,老年组AQP3 mRNA表达水平为0.316±0.109;2.青年组AQP3蛋白表达水平为1.936±0.250,中年组1.813±0.224,老年组1.044±0.271。我们发现老年组皮肤中AQP3 mRNA、蛋白的表达量较青年组和中年组均显著性减少(P值均＜0.01)。
第二部分,我们利用消化分离的方法原代培养了正常人非曝光部位皮肤角质形成细胞和成纤维细胞,进行了细胞鉴定后分别检测了两种细胞不同年龄段AQP3的表达,结果显示:1.角质形成细胞中,青年组AQP3 mRNA表达水平为1.240±0.205,中年组AQP3 mRNA表达水平为0.889±0.136,老年组AQP3 mRNA表达水平为0.392±0.083。AQP3mRNA表达随年龄增加而减少。角质形成细胞中AQP3蛋白表达水平为:青年组1.303±0.231,中年组0.980±0.164,老年组0.360±0.142,AQP3蛋白表达亦随年龄增加而减少。2.成纤维细胞中,青年组AQP3mRNA表达水平为0.881±0.118,中年组AQP3 mRNA表达水平为0.757±0.167,老年组AQP3 mRNA表达水平为0.285±0.143。免疫细胞化学示AQP3蛋白表达水平为:青年组:0.378±0.123,中年组:0.355±0.112,老年组:0.171±0.060。WB示成纤维细胞中AQP3蛋白表达水平为:青年组0.792±0.092,中年组0.692±0.155,老年组0.375±0.112。老年组成纤维细胞AQP3 mRNA、蛋白的表达量较青年组和中年组均显著性减少(P值均＜0.01)。3.青年组角质形成细胞AQP3mRNA、蛋白表达明显高于青年组成纤维细胞(P值均＜0.01),中年组角质形成细胞AQP3蛋白表达明显高于中年组成纤维细胞(P＜0.05),老年组角质形成细胞AQP3 mRNA、蛋白表达与老年组成纤维细胞无显著性差异。
综上所述:AQP3在皮肤组织及体外原代培养的角质形成细胞、成纤维细胞中的表达与年龄有关。AQP3的表达下降与皮肤自然衰老有关。
Aging means that organs' adaptability decreases accompanied with years of age, and human is liable to diseases or death. Aging is regulated by presumptive genes, as well as exterior and interior's abrasions and consume, which are both shown in cell and molecular level. Skin is located in body surface, skin aging comprise natural aging and photoaging. Mechanism of natural aging is not clear, the representative theory include gene regulation theory、free radical theory、metabolic disorder theory. Gene regulation is fundamental of skin natural aging.
One of feature of the clinical manifestation of skin natural aging is xerosis cutis、desquamating、fragility increasing, and recovery hypofunction; the histological manifestation include skin thinning、epidermal renewal stepping down、stratum corneum's barrier and hydration function descending. The normal water content of stratum corneum retained between 10%-20%, which make skin soft; but in old man, the water content of skin is 75% compared normal content, which cause xerosis cutis. Meanwhile,water content of skin cells decrease, which cause tiny shrinkage and enzymatic active decrease. Thus, skin aging is concerned with water content、stratum corneum's barrier and hydration function.
AQP is a kind of membrane integral protein which can fast transport water. AQP has 13 hypotype in mammalian, which are distributed in different tissue and cell. According to the different function of AQPs, AQPs are divided into two subfamily: aquaporins and aquaglyceroporins. The former transport only water; aquaglyceroporins transport not only water but also glycerol. AQP3 is a aquaglyceroporin which is located in skin. AQP3 participate in several patho-physiological functions including urine concentration、water balance of air tube surface、intestinal tract's water absorption. In dermal patho-physiological course, AQP3 can transport water and glycerol to epiderm, so AQP3 is significant to epidermal barrier and water retention. Researchers found AQP3-/- mouse display xerosis cutis、stratum corneum's barrier function descending、skin elasticity descending、skin barrier repairing delayed、and biosynthesis damage、wound healing delay. All of these hint that AQP3 participate skin aging.
In order to identify the relationship between AQP3 and skin aging, we detect the expression of AQP3 mRNA and protein of different ages by RT-PCR and Western blot. The result display: 1 .AQP3 mRNA in teenage group: 0.654±0.104, in middle-age group: 0.685±0.143,in old- age: 0.316±0.109. 2.The expression of AQP3 protein in in teenage group: 1.936 +0.250, in middle-age group: 1.813±0.224,in old- age: 1.044 + 0.271. We found AQP3 mRNA and protein in old-age group significantly lower than the level of middle-age group (P<0.01), and teenage group(P＜0.01)
In the second part, normal human epidermal keratinocytes and skin fibroblast of different ages were cultured; the expression of AQP3 was investigated in keratinocytes and fibroblast respectively. The result display: 1 .in keratinocytes, AQP3 mRNA in teenage group: 1.240±0.205, in middle-age group: 0.889±0.136,in old- age: 0.392±0.083. The expression of AQP3 protein in in teenage group: 1.303±0.231, in middle-age group: 0.980±0.164,in old- age: 0.360 + 0.142. AQP3mRNA and protein in old-age group keratinocytes decreased with the increase of age. 2. In fibroblast, AQP3 mRNA in teenage group: 0.881±0.118, in middle-age group: 0.757±0.167,in old- age: 0.285±0.143. The expression of AQP3 protein by WB in teenage group: 0.792±0.092, in middle-age group: 0.692±0.155,in old- age: 0.375 + 0.112. AQP3 mRNA and protein in old-age group fibroblast decreased significantly (P<0.01). 3. AQP3 mRNA and protein in keratinocytes of teenage group is signify-cantly higher than fibroblasts of teenage group(P＜0.01). AQP3 protein in keratinocytes of middle-age group is significantly higher than fibroblasts of middle-age group(P<0.05). AQP3 mRNA and protein of old-age group in keratinocytes and fibroblasts is not significantly different.
ALL findings suggest the expression level of AQP3 in the human skin is associated with age, and decreases as the age grow. AQP3 may play a important role in aging of human skin.
引文
[1]Goihman-Yahr M.Skin aging and photoaging:an outlook.Clin Dermatol.1996Mar-Apr;14(2):153-60
[2]赵辨主编.临床皮肤病学.南京:江苏科学技术出版社,2001.275-277
[3]Molognia W,Carliste K.Structural changes in ageing skin.Br J Derma tol,1990,(supp135):61-70
[4]Uitto J.Understanding premature skin aging.N Engl J Med,1997:1463-1465
[5]Uitto J,Bernstein EF.Molecular mechanisms of cutaneous aging:Connective tissue alterations in thedermis.J invest Dermatol,1998:41-44
[6]Kagan VE,Kisin ER,Kawai K,et al.Toward mechanism based antioxidant interventions:lessons from natural antioxidants.Ann NY Acar Sci,2002,959:188-198
[7]Spiering AL,Pereira- Smith OM,Smith JR.Correlation between complementation group for immortality and DNA synthesis inhibitors.Exp Cell Res,1991,195(2):541-545
[8]Isobe K,Ito S,Hosaka H,et al.Nuclear- recessive mutations of factors involved in mitochondrial translation are responsible for age- related respiration deficiency of human skin fibroblasts.Biol Chem,1998,273(8):4601-4606
[9]Chung JH,Seo JY,Choi HR,et al.Moduation of skin collagen metabolism in aged and photoaged human skin in vivo.Invest Dermatol,2001,117(5):1218-1224
[10]Gilchrest BA,Garmyn M,Yaar M.Aging and photoaging affect gene expression in cultured human keratinocyte.Arch Dermatol,1994,130:82-86
[11]Isobe K,Ito S,Hosaka H,et al.Nuclear recessive mutations of factors involved in mitochondrial translation are responsible for age related respiration deficiency of human skin fibroblasts.J Biol Chem,1998,273(8):4601-4606
[12]Chung JH,Seo JY,Choi HR,et al.Modulation of skin collagen metabolism in aged and photoaged human skin in vivo.J Invest Dermatol,2001,117(5):1218-1224
[13]Goukassian D,Gad F,Yaar M,et al.Mechanisms and implications of the age associated decrease in DNA repaircapacity.FASEB J,2000,14(10):1325-1334
[14]PrestonG M,AgreP.Molecular cloning of the red cell integral protein of Mr 28,000: A member of an ancient channel family. Proc Natl Acad Sci USA 1991; 88: 11110-14
[15] MoIishitaY, Sakube Y, Sasaki S. et al. Molecular mechanisms and drug development in aquaporin water channel diseases: aquaporin super family(superaquaporins): expansion of aquaporins restricted to multicelular organisms. J Pharmacol Sci. 2004, 96: 276-279
[16] Agre P, King LS, Yasui M, et al. Aquaporin water channels-from atomic structure to clinical medicine. J Physiol. 2002, 542: 3-16
[17] Sui H, Han BG, Lee JK, et al. Structural basis water-specific transport through the AQP1 water channel[J].Nature, 2001, 414(66):872-878.
[18] Bedford JJ, Leader JP, Walker RJ, et al. Aquaporin expression in normal human kidney and in renal disease. J Am Soc Nephrol.2003;14:2581-2587
[19] Song Y, J ayaraman S ,Yang B ,et al. Role of aquaporin water channels in airway fluid transport, humidification and surface liquid hydration. J Gen Physiol, 2003, 117:573-582
[20] Gabazza EC , Kasper M, Ohta K,et al. Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the mouse. Pathol Int ,2004 ,54 (10):774-780
[21] Tsang KW, Leung JC , Tipoe GL ,et al. Down-regulation of aquaporin 3 in bronchiectatic airways in vivo. Respir Med ,2003 ,97 (1) :59-64
[22] Longatti PL , Basaldella L, Orvieto E , et al. Choroid plexus and aquaporin 1: a novel explanation of cerebrospinal fluid production. Pediatr Neurosurg ,2004 ,40 (6): 277
[23] Saadoun S , Papadopoulos MC , Watanabe H, et al. Involvement of aquaporin4 in astroglial cell migration and glial scar formation[J ]. J Cell Sci ,2005 ,118 (24) :5691
[24] Binder DK, Oshio K, Ma T, et al. Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport.2004;15 :259-262
[25] Da T, Verkman AS, Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia. Invest Ophthalmol Vis Sci.2004;45 :4477-4483
[26] Papadopoulos MC, Manley GT, Krishna S ,et al .Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. Faseb J .2004; 18 : 1291-1293
[27]Ma T,Hara M,Sougrat T,et al.Impaired stratum comeum hydration in mice lacking epidermal water channel aquaporin-3.J Biol Chem.2002;277:17147-17153.
[28]Hara M,Verkman AS.Glycerol replacement corrects defective skin hydration,elasticity,and barrier function in aquaporin-3-deficient mice.Proc Natl Acad Sci USA.2003;100:7360-7365.
[29]Segre JA.Epidermal barrier formation and recovery in skin disorders.J Clin Invest,2006,116(5):1150-1158
[30]Rawlings AV,Harding CR.Moisturization and skin barrier function.Dermatol Ther,2004,17(Suppl 1):43-48
[31]王强,张国成.光老化预防和防治的新进展.国外医学皮肤性病学分,2001,27(2):83-85
[32]Warner RR.Electron probe analysis of human skin.J Invest Dermatol,1988,90:218-224.
[33]Segre JA.Epidermal barrier formation and recovery in skin disorders.J Clin Invest,2006,116(5):1150-1158
[34]Rawlin AV,Harding CR.Moisturization and skin barrier function.Dermatol Ther,2004,17(Suppl 1):43-48
[35]Ishibashi K,Yamauchi K,Kageyama Y,et al.Molecular characterization of human Aquaporin-7 gene and its chromosomal mapping.Biochimi Biophys Acta,1998,1399:62-66
[36]Nielsen S,Frokliaer J,Marples D,et al.Aquaporins in the kidney:from molecules to medicine.Physiol Rev.2002.82:205-244.
[37]Jung JS,Preaton GM,Smith BL,et al.Molecular structure of the water channel through aquaporin CHIP,The hourglass model.J Biol Chem,1994,269:14648-14654
[38]Agre P,Bonhivers M,Borgnia MJ.The Aquaporins,Blueprints for cellular plumbing system.JBiol Chem,1998,273:14659-14662
[39]Kozono D,Masato Y,King LS,et al.Aquaporin water channels:atomicstructure and molecular dynamics meet clinical medicine.Clin Invest,2002,109:1395-1399.
[40]Ma T,Song Y,Yang B,et al.Nephrogenic diabetes insipidus in mice lacking Aquapoin-3 water channels. Proc Natl Acad Sci USA, 2000, 97(8):4386-4391
[41 ] Yang B, Ma T, Verkrman As, et al. Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3.J Biol chem, 2001,276(1):624-628
[42] Song Y, J ayaraman S ,Yang B ,et al. Role of aquaporin water channels in airway fluid transport, humidification and surface liquid hydration. J Gen Physiol, 2003, 117:573-582
[43] Itoh A, Tsujikawa T, Fujiyama Y,et al. Enhancement of aquaporin-3 by vasoactive intestinal polypeptide in a human colonic epithelial cell line. Gastroenterol Hepatol.2003; 18(2) :203-10
[44] Varadaraj K, Kumari S, Shiels A, et al. Regulation of aquaporin water permeability in the lens. Invest Ophthalmol Vis Sci, 2005, 46(4): 1393-402
[45] Levin MH, Verkman AS. Aquaporin-dependent water permeation at the mouse ocular surface: in vivo microfluorimetric measurements in cornea and conjunctiva. Invest Ophthalmol Vis Sci, 2004, 45(12):4423-32
[46] Sougrat R, Morand M, Gondran C, et al. Functional expression of AQP3 in human epidermis and keratinocyte cell cultures . Mol Biol Cell. 1998;9:499
[47] Thomas Z, Dan A K. Transport of water and glycerol in Aquaporin 3 is gated by H~+. J Biol Chem, 1999, 274: 21631-21636
[48] Ohman H, Vahlquist A. In vivo studies concerning a PH gradient in human stratum corneum and upper epidermis. Acta Dem Venereol, 1994,74:375-379
[49] Jamot MB, Sougrat R, Taihardat M, et al. Expressin and function of aquaporins in human skin: Is aquaporin-3 just a glycerol transporter? Biochimica et Biophysica Acta, 2006,1758:1034-1042
[50] Hara-Chikuma M, Verkman AS. Aquapoin-3 functions as a glycerol transporter in mammalian skin. Biol Cell, 2005,97(7): 479-486
[51] Sugiyama Y, Ota Y, Hara M, et al. Osmotic stress up-regulate aquaporin-3 expression in cultured human keratinocytes. Biochem Biophys Acta. 2001; 1522:82-88
[52] Gasser P, Lati E, Dumas M. Induction of aquaporine-3 expression and filaggrin degradation in human epidermis after skin barrier disruption [abstract]. J Invest Dermatol. 2004; 123:2. Abstract 11
[53] Choi EH, Man MQ, Wang F, et al. Is endogenous glycerol a determinant of stratum corncum hydration in humans?.J Invest Dermatol,2005,125(2):288-293
[54]Fluhr JW,Mao- Qiang M,Brown BE,et al.Glycerol regulates stratum corneum hydration in sebaceous gland deficient(asebia)mice.J Invest Dermatol,2003,120(5):728-737
[55]M.Hara,T.Ma,A.S.Verkman.Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration,elasticity,and barrier recovery.J Biol Chem.277(2002):46616-46621
[56]Marc Dumas,Neil S.Sadick,Emmanuelle Noblesse,et al.Hydrating skin by stimulating biosynthesis of aquaporins.J Drugs Dermatol.2007 Jun;6(6 Suppl):s20-4
[57]Obeid LM,V enable M E.Signal transduction in cellular senescence.J AM Geriatr Soc,1997;45(3):361-366
[58]Goldstein S.Replicative senescence:the fibroblast comes of age.Science,1990;249(4973):1129-1133
[59]黄英,张宗玉,童坦君.人衰老成纤维细胞凋亡的可诱导性[J],中华老年医学杂志,2000,19(3):170-173
[60]OSTLER E L,WALLIS C V,ABOALCHAMAT B,et al.Telomerase and the cellular lifespan:implication of the aging process.J Pediatr Endocrinol Metab,2000,13(Suppl 6):1467-1476
[61]Turner R,Tijian R.Leucine repeats and an adjacent DNA bingding domain mediates the formation of functional c-fos:c-jun heterodiamer.Science,1989,243(4899):1689-1694
[62]Garmyn M.Influence of aging on gene expression in culture human keratinocyte.Clin Res,1991,39(Suppl):525A
[63]Rachid Sougrat,Maryse Morand,Catherine Gondran,et al.Functional Expression of AQP3 in Human Skin Epidermis and Reconstructed Epidermis.Society for Investigative Dermatology,2002,118(4):678-685
[64]Verdier-Sevrain S,Bonte F.Skin hydration:a review on its molecular mechanisms.J Cosmet Dermatol.2007 Jun;6(2):75-82
[65]Boury-Jamot M,Sougrat R,Tailhardat M,et al.Expression and function of aquaporins in human skin is aquaporine-3:Is aquaporin-3 just a glycerol transporter? Biochim Biophys Acta.2006;1758:1034-1042
[66] Mirza R, Hayasaka S, Kambe F, et al. Increased expression of aquaporin-3 in the epidermis of DHCR24 knockout mice. Br J Dermatol. 2008 Apr;158(4):679-84. Epub 2008 Jan 30
[67] Mariko Hara-Chikumal , A. S. Verkman. Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing . J Mol Med, 2008 Feb; 86(2):221-31
[68] Hara-Chikuma M, Verkman AS. Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol. 2008 Jan;28(1):326-32
[69] Cong CAO, Yun SUN, Sarah HEALEY,et al. EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. Biochem. J. 2006 (400), 225-234
[70] Bellemere G, Von Stetten O, Oddos T. Retinoic acid increases aquaporin 3 expression in normal human skin. J Invest Dermatol. 2008 Mar;128(3):542-8.
[71] Cao C, Wan S, Jiang Q, et al. All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. J Cell Physiol. 2008 May;215(2):506-16
[1]HuangC,ThompsonTE.Properties of lipid bilayer membranes separating two aqueous Phases:water Permeability.J Mol Biol,1966,15:539-554
[2]Saboori A M,Smith B L,Agre P.Polymorphism in the Mr 32,000 Rh protein purified from Rh(D)-positive and -negative erythrocytes.Proc Natl Acad Sci USA 1988;85:4042-45
[3]DenkerB M,SmithB L,K uhajda F P,et al.Identification,purification,and characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules.J Biol Chem 1988;263:15634-42
[4]PrestonG M,AgreP.Molecular cloning of the red cell integral protein of Mr 28,000:A member of an ancient channel family.Proc Natl Acad Sci USA 1991;88:11110-14
[5]Preston G M,Carroll T P,Guggino W B,et al.Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein.Science,1992,256(5055):385-7
[6]Morishita Y,Sakube Y,Sasaki S,et al.Molecular mechanisms and drug development in aquaporin water channel diseases:aquaporin super family(super aquaporins):expansion of aquaporins restricted to multi-cellular organisms.J Pharmacol Sci.2004;96:276-279
[7]Moon C,Preeston GM,Griffin CA,et al.The aquaporin-CHIP28 gene:structure,organization and chromsomal localization.J Biol Chem,1993,268:1577-15778
[8]Ishibashi K,Yamauchi K,Kageyama Y,et al.Molecular characterization of human Aquaporin-7 gene and its chromosomal mapping.Biochimi Biophys Acta,1998,1399:62-66
[9]Iu M,Lee MD,Smith BL,et al.The human AQP4 gene:definition of the locus encoding tow water channel polypeptides in brain.Proc Natl Acad Sci USA,1996,93:10908-109012
[10] Lee MD, Bhakta KY,Raina S ,et al. The human Aquaporin-5 gene molecular characterization and chromosomal localization. J Biol Chem,1996,271:8599-8604.
[11] Viggiano L, Rocchi M, Svetto M, et al. Assignment of the aquaporin-8 water channel gene(AQP8) to human chromosome 16pl2.Cytogen cell genet, 1999,84:208-221
[12] Shi LB, Skach WR, MaT, et al. Distinct biogenesis mechanisms for the water channels MIWC and CHIP28 at the endoplasmic reticulum. Biochemistry, 1995, 34: 8250-8256
[13] Jung JS, Preaton GM, Smith BL, et al. Molecular structure of the water channel through aquaporin CHIP, The hourglass mode1. J Biol Chem, 1994,269: 14648-14654.
[14] Agre P, Bonhivers M, Borgnia MJ. The Aquaporins, Blueprints for cellular plumbing system. J Biol Chem, 1998, 273: 14659-4662.
[15] Kozono D, Masato Y, King LS, et al.Aquaporin water channels:atomicstructure and molecular dynamics meet clinical medicine .Clin Invest, 2002, 109: 1395-1399.
[16] Nielsen S, Frokliaer J, Marples D, et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002. 82: 205-244.
[17] Verkman AS,Vanhoek AN,Ma TH, et al .Water transport across mammalian cell membranes. Am J Physiol,1996,270(1Pt1):C12-30
[18] Verbavatz JM, Brown D, Sabolic I, et al. Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: a freeze-fracture study. J Cell Biol, 1993, 123(3):605-18.
[19] Smith BL, Agre P. Erythrocyte Mr 28000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins. J Biol Chem, 1991, 266: 6407-6415.
[20] Verkman AS. Renal concentrating and diluting function in deficiency of specific aquaporin geng. Exp Nephrol,2002,10(4):235-240
[21] Sui H, Han BG, Lee JK, et al. Structural basis water-specific transport through the AQP1 water channel[J].Nature, 2001, 414(66):872-878.
[22] Bedford JJ, Leader JP, Walker RJ, et al. Aquaporin expression in normal human kidney and in renal disease. J Am Soc Nephrol.2003;14:2581-2587
[23] Pallone TL, Edwards A, Ma T, et al. Requirement of aquaporin-1 for NaCl-driven Water across descending vasa recta. J Clin lnvest, 2000, 105(2):215-222
[24] Ma T, Song Y, Yang B, et al. Nephrogenic diabetes insipidus in mice lacking Aquapoin-3 water channels. Proc Natl Acad Sci USA, 2000, 97(8):4386-4391
[25] Yang B, Ma T, Verkrman As, et al. Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3.J Biol chem,2001,276(1):624-628
[26] Chou C L, Ma T, Yang B, et al. Fourfold reduction of water permeability in inner medullary collecting duct of aquaporin-4 knockout mice. Am J Physiol. 1998,274(2Pt1): C549-54
[27] Nielsen S, Frokiaer J, marples D, et al.Aquaporins in the kidney: from molecules to medicine .Physiol Rev 2002;82(1):205
[28] Calamita G, Ferri D, Gena P,et al. The inner mitochondrial membrane has aquaporin-8 water channels and is highly permeable to water. J Biol Chem, 2005, 280:17149-17153
[29] Desagher S, Martinou JC. Mitochondria as the central control point of apoptosis/Trends Cell Biol, 2000, 10:369-377
[30] Kreda SM, Gynn MC , Fenstermacher DA, et al. Eqr-ession and localization of epithelial aquaorins in the odult human-lung. AM J Respir Cell Mol Biol ,2001 ,24 (3) :224-234.
[31] King LS ,Nielsen S ,Agre P. Aquaporins and the respiratory system: advice for a lung investigator. J Clin Invest ,2000 ,105 (1): 15-16.
[32] Wellner RN , Hoque ST, Goldsmith CM ,et al. Evidence that aquaporin-8 is located in the basolateral membrane if rat submandibular gland acinar cells . Pfugers Arch, 2000 ,441 :49-56.
[33] Elkjaer ML ,Nejsum LN , Gresz V , et al. Immunolocalization of aquaporin 8 in rat kidney, liver, testis , epidedymis, jeju-num ,colon, principal bronchi and salivary glands . Am J Physiol Renal Physiol, 2001 ,281 (6): 1047-1057.
[34] Song Y, J ayaraman S ,Yang B ,et al. Role of aquaporin water channels in airway fluid transport, humidification and surface liquid hydration. J Gen Physiol, 2003, 117:573-582
[35] Song Y, Ma T, Mathay MA ,et al. Role of aquaporin-4 in air-space-to-capollaru ater permeability in intact mouse lung measured by a novel gravimetric method. J Gen Physoil ,2000 ,155 (1): 17-27
[36] Bai C , Fukuda N, Song Y,et al. Lung fluid transort in aquapoein-1 and aquaporin-4 knockout mice . J Clin Invest ,1999 ,103 (4) :555-561
[37] Ma T ,Fukuda N ,Song Y,et al. Lung fluid t ransport in aquapoein-5 knockout mice . J Clin Invest ,2000 ,105 (1): 93-100
[38] King LS. Decreased pulmonary vascular permeability in aquaporin-1-null humans. Proc Natl Acad Sci ,2002 ,99 :1059-1063
[39] Umenishi F ,Cater P ,Yang B. Sharp increase in rat ling water channel expression in the perinaal period Am. J Respir Cell Mol Biol ,1996 ,15 :3 - 11
[40] Song Y,Verkman AS. Aquaporin-5 dependent fluid secretion in airway submucosal glands . J Biol Chem, 2001 ,276 :41288-41292
[41] Towne JE, Harrod Ks, Krane CM, et al. Decreased expression of AQP1 and AQP5 in mouse after acute viral infection. Am J respire Cell Mol Biol, 2000, 22:33-44
[42] Gabazza EC , Kasper M , Ohta K,et al. Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the mouse. Pathol Int ,2004 ,54 (10):774-780
[43] Tsang KW, Leung JC , Tipoe GL ,et al. Down-regulation of aquaporin 3 in bronchiectatic airways in vivo. Respir Med ,2003 ,97 (1): 59-64
[44] Saadoun S ,Verkman AS. Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature ,2005 ,434 :786-792
[45] Xiang Y, Ma B , Li T ,et al. Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis . Acta Pharmacol Sin ,2004 ,25 (6) :812-816
[46] Matsuzald T, TajikaY, Ablimit A, et al. Aquaporins in the digestive systerm . Med Electron Microsc, 2004.37(2):71-80
[47] Ma T ,Jayaraman S ,Wang KS,et al. Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels. Am J Physiol Cell Physiol,2001,280( 1 ):C 126-34
[48] Silbersldn C, Kjerbel A, Amodo G, et al. Functional characterization and Localization of AQP3 in the human colon. Braz J Med Biol Res, 1999, 32(10): 1303-1313
[49] Itoh A, Tsujikawa T, Fujiyama Y,et al. Enhancement of aquaporin-3 by vasoactive intestinal polypeptide in a human colonic epithelial cell line. Gastroenterol Hepatol.2003; 18(2):203 -10
[50] Wang KS ,Ma T ,Filiz F , et al. Colon water transport in transgenic mice lacking aquaporin-4 water channels . Am J Physiol Gastrointest Liver Physiol ,2000 ,279(2) :G463-470
[51] Krane CM, Melvin JE, Nguyen HV, et al. Salivary acinar cells from aquaporin 5 deficient mice have decreased membrane water permeability and altered cell volume regulation. J Biol Chem, 2001,276: 234313-2340
[52] Matsuki M,Hashimoto S ,Shimono M, et al. Involvement of aquaporin-5 water channel in osoregulation in parotid secretory granules. Membr Biol ,2005 , 203 (3) :119-126
[53] Yang B, Song Y, Zhao D,Verkman A S .Phenotype analysis of aquaporin-8 null mice. Am J Physiol Cell Physiol, 2005, [Epub ahead of print]
[54] Venero JL , Vizuete ML , Machado A , et al. Aquaporins in the central nervous system. Prog Neuro biol ,2001 ,63 (3) :321 - 336
[55] Longatti PL, Basaldella L, Orvieto E , et al. Choroid plexus and aquaporinl: a novel explanation of cerebrospinal fluid production. Pediatr Neurosurg ,2004 ,40 (6): 277
[56] Moon Y, Hong SJ , Shin D , et al. Increased aquaporinl expression in choroid plexus epithelium after systemic hyponatremia. Neuro sci Lett ,2006 ,395 (1) :1
[57] Solenov EL,Vetrivel L, Oshio K ,et al. Optical measurement of swelling and water transport in spinal cord slices from aquaporin null mice. J Neurosci Methods. 2002; 113:85-90
[58] Verkman A S. More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci, 2005; 118:3225-3232
[59] Saadoun S , Papadopoulos MC , Watanabe H, et al. Involvement of aquaporin4 in astroglial cell migration and glial scar formation[J ]. J Cell Sci ,2005 ,118 (24): 5691
[60] Hiroaki Y, Tani K, Kamegawa A, et al. Implications of the aquaporin4 structure on array formation and cell adhesion[J ]. J Mol Biol ,2006 ,355 (4) :628
[61] Papadopoulos MC, Manley GT, Krishna S ,et al .Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. Faseb J.2004;18:1291-1293
[62] Binder DK, Oshio K, Ma T, et al. Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport.2004;15 :259-262
[63] Da T, Verkman AS, Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia. Invest Ophthalmol Vis Sci. 2004;45 :4477-4483
[64] HuangD, ChenP ,ChenS, et al. Expression patterns of aquaporins in the inner ear: evidence for concerted actions of multiple types of aquaporins to facilitate water transport in the cochlea. Hear Res.2002;165:85-95
[65] Nagelhus EA, Mathiisen TM, Ottersen OP, et al. Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience.2004; 129:905-913
[66] Verman AS. Role of aquaporin water channels in eye function. Exp Eye Res. 2003,76:137-143
[67] Berry V, Francis P, Kaushal S, et al. Missense underlie autosomal dominant 'polymorphic'and lamellar cataracts linked tol2q[J]. Nat Genet, 2000, 25(1):15-7
[68] Hasegawa H, Lian SC, Finkbeiner WE, et al. Extra renal tissue distribution of CHIP28 water channels by in situ hybridization and antibody staining[J]. Am J Physiol, 1994,266(4):C893-903
[69] Frigeri A, Cropper MA, Turck CW, et al. Immunolocalization of the mercurial- Insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes. Proc Natl Acad sci USA, 1995, 92(10):4328-31
[70] Thiagarajah JR, Verkman AS. Aquaporin deletion in mice reduces corneal water permeability and delays restoration of transparency after swelling. J Biol Chem, 2002,277(21):19139-4
[71] Varadaraj K, Kumari S, Shiels A, et al. Regulation of aquaporin water permeability in the lens. lnvest Ophthalmol Vis Sci, 2005, 46(4): 1393-402
[72] Levin MH, Verkman AS. Aquaporin-dependent water permeation at the mouse ocular surface: in vivo microfiuorimetric measurements in cornea and conjunctiva. Invest Ophthalmol Vis Sci, 2004, 45(12):4423-32
[73] Iandiev I, Pannicke T, Reichel MB, et al. Expression of aquaporin-1 immunoreactivity by photoreceptor cells in the mouse retina .Neurosci Lett, 2005, 388(2):96-99
[74] Yang H, Reinach PS, Koniarek JP, et al. Fluid transport by cultured corneal epithelial celll layers[J]. Br J Ophthalmol, 2000, 84(2):199-204
[75] Patil RV, Han Z, Yiming M, et al. Fluid transport by human nonpigmented ciliary epithelial layers in culture: a homeostatic role for aquaporin-1. Am J Physiol Cell Physiol, 2001, 281(4): C1139-45
[76] Ohashi Y, Ishida R, Kojlma T, et al. Abnormal protein profiles in tears with dry eye syndrome.Am J Ophthalmol, 2003, 136(2):291-299
[77] Zhang D, Vetrivel L, Verkman AS. Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production. J Gen Physiol, 2002,1999(6): 561-569
[78] Sougrat R, Morand M, Gondran C, et al. Functional expression of AQP3 in human skin epidermis and reconstructed epidermis. J Invest Dermatol. 2002; 118:678-685
[79] Ma T, Hara M, Sougrat T, et al. Impaired stratum corneum hydration in mice lacking epidermal water channel aquaporin-3. J Biol Chem. 2002;277:17147-17153.
[80] Hara M, Verkman AS. Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Proc Natl Acad Sci USA. 2003;100:7360-7365.
[81] Marc Dumas, Neil S. Sadick, Emmanuelle Noblesse, et al. Hydrating skin by stimulating biosynthesis of aquaporins. J Drugs Dermatol. 2007 Jun;6(6 Suppl): s20-4
[82] Cong CAO, Yun SUN, Sarah HEALEY, et al. EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. Biochem. J. 2006 , 400:225-234
[83] Mariko H C, Verkman A S. Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing. J Mol Med. 2008 Feb;86(2):221-31
[84] Olsson M, Broberg A, Jernas M, et al. Increased expression of aquaporin 3 in atopic eczema. Allergy. 2006 Sep;61(9):l 132-7
[85] Boury-Jamot M, Sougrat R, Tailhardat M, et al. Expression and function of aquaporins in human skin is aquaporine-3: Is aquaporin-3 just a glycerol transporter? Biochim Biophys Acta. 2006;1758:1034-1042.
[86] Bellemere G, Von Stetten O, Oddos T. Retinoic acid increases aquaporin 3 expression in normal human skin. J Invest Dermatol. 2008 Mar;128(3):542-8.
[87] Cao C, Wan S, Jiang Q, et al. All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. J Cell Physiol. 2008 May;215(2):506-16
[1]Goihman-Yahr M.Skin aging and photoaging:an outlook.Clin Dermatol.1996Mar-Apr;14(2):153-60.
[2]Anthony V,Benedetto,DO.The environment and skin aging.Clin in Derm,1998,16(1):129-139.
[3]Gilchrest B A,Szabo G,Flynn E.Chronologic and Actinically induced aging in human facial skin.J Invest Derm,1983,80(suppl 1):81-85
[4]Chung J H.Photoaging in Asians.Photodermtol photoimmunol photomed,2003,19(3):109-121
[5]Bernstein EF,Uitto J.The effect of photoaging on dermal extracellular matrix.Clin Dermatol,1996,14(2):143-151
[6]Ei-Domyati M,Attia S,Saleh F,et al.Intrinsic aging vs.photoaging:a comparative histopathological,immnohistochemical,and ultrastructural study of skin.Exp Dermtol,2002,11(5):398-405.
[7]KangS,F isherG J,V oorheesJJ,et al.Photoaging and topical tretinoin.Ar chD ermatol,1997,13 3:1280-1284
[8]Gilchrest BA.A review of skin aging and its medical therapy.Br JDe rmatol,1996,135:8 67-875
[9]DeBuys HV,Levy SB,Murray JC,et al.Modern approaches to photoprotection.Dermatol Clin,2000,18(4):577
[10]Humbert P.Topical vitamin C in the treatment of photoaged skin.Eur Derrnatol.2001 Mar-Apr;11(2):172-3.Review
[11]Lin JY,Selim MA,Shea CR,et al.UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol,2003,48:866-874
[12]Thiele JJ,Traber MG.Packer L.Depletion of human stratum corneum vitamin E:an early and sensitive in vivo marker of UV induced photo-oxidation.J Invest Dermatol.1998 May;110(5):756-61.
[13]Ritter EF.Axelrod M.Minn KW,et al.Modulation of ultraviolet light-induced epidermal damage:beneficial effects oftocopherol.Plast Reconstr Surg.1997 Sep;100(4):973-80
[14]Riceiarelli R,Maroni P,Ozer N,et al.Age—dependent increase of collagenase expression can be reduced by alpha—tecopherol via proteinkinase C inhibition.Free Radic Biol Med,1999,27(7—8):729—737
[15]StaIL W.siesH.Carotenoids and protection against solar UV radiation[J].Skin Pharmacol Appl skin Physiol,2002,15(5):291
[16]Hoppe U,Bergemann J,DiembeckW,et al.Coenzyme Q10,a cutaneous antioxidant and energizer.Biofactom,1999,9(2—4):371-378.
[17]梁建梅.皮肤光老化的外用药物治疗.现代中西医结合杂志,2005,14(19):1193
[18]Mckenzie RC.Selenium,ultraviolet radiation and the skin.Clin ExpDermatol.2000,25(8):631.
[19]Tsukahara K,Moriwaki S,Hotta M,et al.The effect of sunscreen on skin elastase activity induced by ultraviolet-A irradiation.Biol Pharm Bull.2005Dec;28(12):2302-7
[20]陈昆,常宝珠,郑家润,等.抗氧化剂与紫外线相关性皮肤病.国外医学皮肤性病分册:2003,29(6):349-351
[21]Mitani H,Koshiishi I,Sumita T,et al.Prevention of the photodamage in the hairless mouse dorsal skin by kojic acid as an iron chelator.Eur J Pharmacol,2001,411:169-174
[22]Xia J,Song X,Bi Z,Chu W,Wan Y.UV-induced NF-kappaB activation and expression of IL-6 is attenuated by(-)-epigallocatechin-3-gallate in cultured human keratinocytes in vitro.Int J Mol Med.2005 Nov;16(5):943-50
[23]Meeran SM,Mantena SK,Katiyar SK.Prevention of ultraviolet radiation-induced immunosuppression by(-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair.Clin Cancer Res.2006 Apr 1;12(7 Pt 1):2272-80
[24]Luo D,Min W,Lin XF,Wu D,Xu Y,Miao X.Effect of epigallocatechingallate on ultraviolet B-induced photo-damage in keratinocyte Cell line.Am J Chin Med.2006;34(5):911-22
[25]姚煜,田涛,南克俊.白藜芦醇抗衰老免疫机制的研究.中药材,2006.29(5):464-466
[26]Kang S,Cho S,Chung JH,Hammerberg C,etal..Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo.Am J Pathol.2005 Jun;166(6):1691-9
[27]雷小兵,等.全反式维A酸对UVA诱导人成纤维细胞胶原合成的影响.中国皮肤性病学杂志,2004,18(4):202
[28]Lowe N,Gifford M,Tanghetti E,et al.Tazarotene 0.1%cream versus tretinoin 0.05%emollient cream in the treatment of photodamaged facial skin:a multicenter,double-blind,randomized,parallel group study.J Cosmet Laser Ther,2004,6:79-85
[29]Kang S,Leyden JJ,Lowe NJ,et al.Tazarotene cream for the treatment of facial photodamage:a multicenter,investigator-masked,randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks. Arch Dermatol, 2001,137: 1597-1604
[30] Hoick DE, Ng JD.Facial skin rejuvenation. Curr Opin Ophthalmol. 2003 Oct; 14(5):246-52. Review.
[31] Goldman MP, Marchell N, Fitzpatrick RE. Laser skin resurfacing of the face with a combined CO2/Er:YAG laser. Dermatol Surg. 2000 Feb;26(2): 102-4
[32] Rostan EF, Fitzpatrick RE, Goldman MP. Laser resurfacing with a long pulse erbium: YAG laser compared to the 950 ms pulsed CO(2) laser. Lasers Surg Med. 2001 ;29(2): 136-41
[33] YAGHMAI D , GARDEN J M , BAKUS A D , et al. Comparison of a 1064 nm laser and a 1320 nm laser for the nonablative treatment of acne scars. Dermatol Surg, 2005 ,31 (8 Pt 1)-.903-909
[34] BITTER P H. Noninvasive rejuvenation of photodamaged skin using serial, full - face intense pulsed light treatments. Dermatol Surg, 2000 ,26(9) :835 -842
[35] WEISS R A, WEISS M A, BEASL EY K L. Rejuvenation of photoaged skin : 5 years results with intense pulsed light of the face , neck , and chest. Dermatol Surg, 2002 ,28 (12) :1115-1119
[36] SADICK N S , WEISS R, KILMER S , BITTER P. Photorejuvenation with intense pulsed light: results of a multi - center study. J Drugs Dermatol, 2004 ,3(1): 41-49
[37] WEISS R A, WEISS M A, MUNAVALL I G, et al. Monopolar radiofrequency facial tightening : a retrospective analysis of efficacy and safety in over 600 treatments. J Drugs Dermatol, 2006 ,5 (8) :707 - 712
[38] RUSSELL B A, KELL ETT N , REILL Y L R. A study to determine the efficacy of combination L ED light therapy (633 nm and 830 nm) in facial skin rejuvenation. J Cosmet Laser Ther, 2005 ,7 (3-4) :196 - 200
[39] Hernandez-Perez E, Ibiett EV Gross and microscopic findings in patients undergoing microdermabrasion for facial rejuvenation Dermatol Surg. 2001 Jul;27(7):637-40
[40] Spencer JM Microdermabrasion. Am J Clin Dermatol.2005;6(2):89-92
[41] Briden ME. Alpha-hydroxyacid chemical peeling agents: case studies and rationale for safe and effective use Cutis. 2004 Feb;73(2 Suppl): 18-24
[42]Zakopoulou N,Kontochristopoulos G..Superficial chemical peels.J Cosmet Dermatol.2006 Sep;5(3):246-53
[43]Fagien S,Klein AW.A brief overview and history of temporary fillers:evolution,advantages,and limitations.Plast Reconstr Surg.2007;120(6 Suppl):8S-16S
[44]Dastoor SF,Misch CE,Wang HL.Dermal fillers for facial soft tissue augmentation.J Oral Implantol.2007;33(4):191-204
[45]Beer K,Waibel J.Botulinum toxin type A enhances the outcome of fractional resurfacing of the cheek.J Drugs Dermatol.2007;6(11):1151-2
[46]Kaplan SE,Sherris DA,Gassner HG,et al.The use of botulinurn toxin A in perioral rejuvenation.Facial Plast Surg Clin North Am.2007;15(4):415-21,ⅴ-ⅵ
[2]赵辨主编.临床皮肤病学.南京:江苏科学技术出版社,2001.275-277
[3]Molognia W,Carliste K.Structural changes in ageing skin.Br J Derma tol,1990,(supp135):61-70
[4]Uitto J.Understanding premature skin aging.N Engl J Med,1997:1463-1465
[5]Uitto J,Bernstein EF.Molecular mechanisms of cutaneous aging:Connective tissue alterations in thedermis.J invest Dermatol,1998:41-44
[6]Kagan VE,Kisin ER,Kawai K,et al.Toward mechanism based antioxidant interventions:lessons from natural antioxidants.Ann NY Acar Sci,2002,959:188-198
[7]Spiering AL,Pereira- Smith OM,Smith JR.Correlation between complementation group for immortality and DNA synthesis inhibitors.Exp Cell Res,1991,195(2):541-545
[8]Isobe K,Ito S,Hosaka H,et al.Nuclear- recessive mutations of factors involved in mitochondrial translation are responsible for age- related respiration deficiency of human skin fibroblasts.Biol Chem,1998,273(8):4601-4606
[9]Chung JH,Seo JY,Choi HR,et al.Moduation of skin collagen metabolism in aged and photoaged human skin in vivo.Invest Dermatol,2001,117(5):1218-1224
[10]Gilchrest BA,Garmyn M,Yaar M.Aging and photoaging affect gene expression in cultured human keratinocyte.Arch Dermatol,1994,130:82-86
[11]Isobe K,Ito S,Hosaka H,et al.Nuclear recessive mutations of factors involved in mitochondrial translation are responsible for age related respiration deficiency of human skin fibroblasts.J Biol Chem,1998,273(8):4601-4606
[12]Chung JH,Seo JY,Choi HR,et al.Modulation of skin collagen metabolism in aged and photoaged human skin in vivo.J Invest Dermatol,2001,117(5):1218-1224
[13]Goukassian D,Gad F,Yaar M,et al.Mechanisms and implications of the age associated decrease in DNA repaircapacity.FASEB J,2000,14(10):1325-1334
[14]PrestonG M,AgreP.Molecular cloning of the red cell integral protein of Mr 28,000: A member of an ancient channel family. Proc Natl Acad Sci USA 1991; 88: 11110-14
[15] MoIishitaY, Sakube Y, Sasaki S. et al. Molecular mechanisms and drug development in aquaporin water channel diseases: aquaporin super family(superaquaporins): expansion of aquaporins restricted to multicelular organisms. J Pharmacol Sci. 2004, 96: 276-279
[16] Agre P, King LS, Yasui M, et al. Aquaporin water channels-from atomic structure to clinical medicine. J Physiol. 2002, 542: 3-16
[17] Sui H, Han BG, Lee JK, et al. Structural basis water-specific transport through the AQP1 water channel[J].Nature, 2001, 414(66):872-878.
[18] Bedford JJ, Leader JP, Walker RJ, et al. Aquaporin expression in normal human kidney and in renal disease. J Am Soc Nephrol.2003;14:2581-2587
[19] Song Y, J ayaraman S ,Yang B ,et al. Role of aquaporin water channels in airway fluid transport, humidification and surface liquid hydration. J Gen Physiol, 2003, 117:573-582
[20] Gabazza EC , Kasper M, Ohta K,et al. Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the mouse. Pathol Int ,2004 ,54 (10):774-780
[21] Tsang KW, Leung JC , Tipoe GL ,et al. Down-regulation of aquaporin 3 in bronchiectatic airways in vivo. Respir Med ,2003 ,97 (1) :59-64
[22] Longatti PL , Basaldella L, Orvieto E , et al. Choroid plexus and aquaporin 1: a novel explanation of cerebrospinal fluid production. Pediatr Neurosurg ,2004 ,40 (6): 277
[23] Saadoun S , Papadopoulos MC , Watanabe H, et al. Involvement of aquaporin4 in astroglial cell migration and glial scar formation[J ]. J Cell Sci ,2005 ,118 (24) :5691
[24] Binder DK, Oshio K, Ma T, et al. Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport.2004;15 :259-262
[25] Da T, Verkman AS, Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia. Invest Ophthalmol Vis Sci.2004;45 :4477-4483
[26] Papadopoulos MC, Manley GT, Krishna S ,et al .Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. Faseb J .2004; 18 : 1291-1293
[27]Ma T,Hara M,Sougrat T,et al.Impaired stratum comeum hydration in mice lacking epidermal water channel aquaporin-3.J Biol Chem.2002;277:17147-17153.
[28]Hara M,Verkman AS.Glycerol replacement corrects defective skin hydration,elasticity,and barrier function in aquaporin-3-deficient mice.Proc Natl Acad Sci USA.2003;100:7360-7365.
[29]Segre JA.Epidermal barrier formation and recovery in skin disorders.J Clin Invest,2006,116(5):1150-1158
[30]Rawlings AV,Harding CR.Moisturization and skin barrier function.Dermatol Ther,2004,17(Suppl 1):43-48
[31]王强,张国成.光老化预防和防治的新进展.国外医学皮肤性病学分,2001,27(2):83-85
[32]Warner RR.Electron probe analysis of human skin.J Invest Dermatol,1988,90:218-224.
[33]Segre JA.Epidermal barrier formation and recovery in skin disorders.J Clin Invest,2006,116(5):1150-1158
[34]Rawlin AV,Harding CR.Moisturization and skin barrier function.Dermatol Ther,2004,17(Suppl 1):43-48
[35]Ishibashi K,Yamauchi K,Kageyama Y,et al.Molecular characterization of human Aquaporin-7 gene and its chromosomal mapping.Biochimi Biophys Acta,1998,1399:62-66
[36]Nielsen S,Frokliaer J,Marples D,et al.Aquaporins in the kidney:from molecules to medicine.Physiol Rev.2002.82:205-244.
[37]Jung JS,Preaton GM,Smith BL,et al.Molecular structure of the water channel through aquaporin CHIP,The hourglass model.J Biol Chem,1994,269:14648-14654
[38]Agre P,Bonhivers M,Borgnia MJ.The Aquaporins,Blueprints for cellular plumbing system.JBiol Chem,1998,273:14659-14662
[39]Kozono D,Masato Y,King LS,et al.Aquaporin water channels:atomicstructure and molecular dynamics meet clinical medicine.Clin Invest,2002,109:1395-1399.
[40]Ma T,Song Y,Yang B,et al.Nephrogenic diabetes insipidus in mice lacking Aquapoin-3 water channels. Proc Natl Acad Sci USA, 2000, 97(8):4386-4391
[41 ] Yang B, Ma T, Verkrman As, et al. Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3.J Biol chem, 2001,276(1):624-628
[42] Song Y, J ayaraman S ,Yang B ,et al. Role of aquaporin water channels in airway fluid transport, humidification and surface liquid hydration. J Gen Physiol, 2003, 117:573-582
[43] Itoh A, Tsujikawa T, Fujiyama Y,et al. Enhancement of aquaporin-3 by vasoactive intestinal polypeptide in a human colonic epithelial cell line. Gastroenterol Hepatol.2003; 18(2) :203-10
[44] Varadaraj K, Kumari S, Shiels A, et al. Regulation of aquaporin water permeability in the lens. Invest Ophthalmol Vis Sci, 2005, 46(4): 1393-402
[45] Levin MH, Verkman AS. Aquaporin-dependent water permeation at the mouse ocular surface: in vivo microfluorimetric measurements in cornea and conjunctiva. Invest Ophthalmol Vis Sci, 2004, 45(12):4423-32
[46] Sougrat R, Morand M, Gondran C, et al. Functional expression of AQP3 in human epidermis and keratinocyte cell cultures . Mol Biol Cell. 1998;9:499
[47] Thomas Z, Dan A K. Transport of water and glycerol in Aquaporin 3 is gated by H~+. J Biol Chem, 1999, 274: 21631-21636
[48] Ohman H, Vahlquist A. In vivo studies concerning a PH gradient in human stratum corneum and upper epidermis. Acta Dem Venereol, 1994,74:375-379
[49] Jamot MB, Sougrat R, Taihardat M, et al. Expressin and function of aquaporins in human skin: Is aquaporin-3 just a glycerol transporter? Biochimica et Biophysica Acta, 2006,1758:1034-1042
[50] Hara-Chikuma M, Verkman AS. Aquapoin-3 functions as a glycerol transporter in mammalian skin. Biol Cell, 2005,97(7): 479-486
[51] Sugiyama Y, Ota Y, Hara M, et al. Osmotic stress up-regulate aquaporin-3 expression in cultured human keratinocytes. Biochem Biophys Acta. 2001; 1522:82-88
[52] Gasser P, Lati E, Dumas M. Induction of aquaporine-3 expression and filaggrin degradation in human epidermis after skin barrier disruption [abstract]. J Invest Dermatol. 2004; 123:2. Abstract 11
[53] Choi EH, Man MQ, Wang F, et al. Is endogenous glycerol a determinant of stratum corncum hydration in humans?.J Invest Dermatol,2005,125(2):288-293
[54]Fluhr JW,Mao- Qiang M,Brown BE,et al.Glycerol regulates stratum corneum hydration in sebaceous gland deficient(asebia)mice.J Invest Dermatol,2003,120(5):728-737
[55]M.Hara,T.Ma,A.S.Verkman.Selectively reduced glycerol in skin of aquaporin-3-deficient mice may account for impaired skin hydration,elasticity,and barrier recovery.J Biol Chem.277(2002):46616-46621
[56]Marc Dumas,Neil S.Sadick,Emmanuelle Noblesse,et al.Hydrating skin by stimulating biosynthesis of aquaporins.J Drugs Dermatol.2007 Jun;6(6 Suppl):s20-4
[57]Obeid LM,V enable M E.Signal transduction in cellular senescence.J AM Geriatr Soc,1997;45(3):361-366
[58]Goldstein S.Replicative senescence:the fibroblast comes of age.Science,1990;249(4973):1129-1133
[59]黄英,张宗玉,童坦君.人衰老成纤维细胞凋亡的可诱导性[J],中华老年医学杂志,2000,19(3):170-173
[60]OSTLER E L,WALLIS C V,ABOALCHAMAT B,et al.Telomerase and the cellular lifespan:implication of the aging process.J Pediatr Endocrinol Metab,2000,13(Suppl 6):1467-1476
[61]Turner R,Tijian R.Leucine repeats and an adjacent DNA bingding domain mediates the formation of functional c-fos:c-jun heterodiamer.Science,1989,243(4899):1689-1694
[62]Garmyn M.Influence of aging on gene expression in culture human keratinocyte.Clin Res,1991,39(Suppl):525A
[63]Rachid Sougrat,Maryse Morand,Catherine Gondran,et al.Functional Expression of AQP3 in Human Skin Epidermis and Reconstructed Epidermis.Society for Investigative Dermatology,2002,118(4):678-685
[64]Verdier-Sevrain S,Bonte F.Skin hydration:a review on its molecular mechanisms.J Cosmet Dermatol.2007 Jun;6(2):75-82
[65]Boury-Jamot M,Sougrat R,Tailhardat M,et al.Expression and function of aquaporins in human skin is aquaporine-3:Is aquaporin-3 just a glycerol transporter? Biochim Biophys Acta.2006;1758:1034-1042
[66] Mirza R, Hayasaka S, Kambe F, et al. Increased expression of aquaporin-3 in the epidermis of DHCR24 knockout mice. Br J Dermatol. 2008 Apr;158(4):679-84. Epub 2008 Jan 30
[67] Mariko Hara-Chikumal , A. S. Verkman. Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing . J Mol Med, 2008 Feb; 86(2):221-31
[68] Hara-Chikuma M, Verkman AS. Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol. 2008 Jan;28(1):326-32
[69] Cong CAO, Yun SUN, Sarah HEALEY,et al. EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. Biochem. J. 2006 (400), 225-234
[70] Bellemere G, Von Stetten O, Oddos T. Retinoic acid increases aquaporin 3 expression in normal human skin. J Invest Dermatol. 2008 Mar;128(3):542-8.
[71] Cao C, Wan S, Jiang Q, et al. All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. J Cell Physiol. 2008 May;215(2):506-16
[1]HuangC,ThompsonTE.Properties of lipid bilayer membranes separating two aqueous Phases:water Permeability.J Mol Biol,1966,15:539-554
[2]Saboori A M,Smith B L,Agre P.Polymorphism in the Mr 32,000 Rh protein purified from Rh(D)-positive and -negative erythrocytes.Proc Natl Acad Sci USA 1988;85:4042-45
[3]DenkerB M,SmithB L,K uhajda F P,et al.Identification,purification,and characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules.J Biol Chem 1988;263:15634-42
[4]PrestonG M,AgreP.Molecular cloning of the red cell integral protein of Mr 28,000:A member of an ancient channel family.Proc Natl Acad Sci USA 1991;88:11110-14
[5]Preston G M,Carroll T P,Guggino W B,et al.Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein.Science,1992,256(5055):385-7
[6]Morishita Y,Sakube Y,Sasaki S,et al.Molecular mechanisms and drug development in aquaporin water channel diseases:aquaporin super family(super aquaporins):expansion of aquaporins restricted to multi-cellular organisms.J Pharmacol Sci.2004;96:276-279
[7]Moon C,Preeston GM,Griffin CA,et al.The aquaporin-CHIP28 gene:structure,organization and chromsomal localization.J Biol Chem,1993,268:1577-15778
[8]Ishibashi K,Yamauchi K,Kageyama Y,et al.Molecular characterization of human Aquaporin-7 gene and its chromosomal mapping.Biochimi Biophys Acta,1998,1399:62-66
[9]Iu M,Lee MD,Smith BL,et al.The human AQP4 gene:definition of the locus encoding tow water channel polypeptides in brain.Proc Natl Acad Sci USA,1996,93:10908-109012
[10] Lee MD, Bhakta KY,Raina S ,et al. The human Aquaporin-5 gene molecular characterization and chromosomal localization. J Biol Chem,1996,271:8599-8604.
[11] Viggiano L, Rocchi M, Svetto M, et al. Assignment of the aquaporin-8 water channel gene(AQP8) to human chromosome 16pl2.Cytogen cell genet, 1999,84:208-221
[12] Shi LB, Skach WR, MaT, et al. Distinct biogenesis mechanisms for the water channels MIWC and CHIP28 at the endoplasmic reticulum. Biochemistry, 1995, 34: 8250-8256
[13] Jung JS, Preaton GM, Smith BL, et al. Molecular structure of the water channel through aquaporin CHIP, The hourglass mode1. J Biol Chem, 1994,269: 14648-14654.
[14] Agre P, Bonhivers M, Borgnia MJ. The Aquaporins, Blueprints for cellular plumbing system. J Biol Chem, 1998, 273: 14659-4662.
[15] Kozono D, Masato Y, King LS, et al.Aquaporin water channels:atomicstructure and molecular dynamics meet clinical medicine .Clin Invest, 2002, 109: 1395-1399.
[16] Nielsen S, Frokliaer J, Marples D, et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002. 82: 205-244.
[17] Verkman AS,Vanhoek AN,Ma TH, et al .Water transport across mammalian cell membranes. Am J Physiol,1996,270(1Pt1):C12-30
[18] Verbavatz JM, Brown D, Sabolic I, et al. Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: a freeze-fracture study. J Cell Biol, 1993, 123(3):605-18.
[19] Smith BL, Agre P. Erythrocyte Mr 28000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins. J Biol Chem, 1991, 266: 6407-6415.
[20] Verkman AS. Renal concentrating and diluting function in deficiency of specific aquaporin geng. Exp Nephrol,2002,10(4):235-240
[21] Sui H, Han BG, Lee JK, et al. Structural basis water-specific transport through the AQP1 water channel[J].Nature, 2001, 414(66):872-878.
[22] Bedford JJ, Leader JP, Walker RJ, et al. Aquaporin expression in normal human kidney and in renal disease. J Am Soc Nephrol.2003;14:2581-2587
[23] Pallone TL, Edwards A, Ma T, et al. Requirement of aquaporin-1 for NaCl-driven Water across descending vasa recta. J Clin lnvest, 2000, 105(2):215-222
[24] Ma T, Song Y, Yang B, et al. Nephrogenic diabetes insipidus in mice lacking Aquapoin-3 water channels. Proc Natl Acad Sci USA, 2000, 97(8):4386-4391
[25] Yang B, Ma T, Verkrman As, et al. Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3.J Biol chem,2001,276(1):624-628
[26] Chou C L, Ma T, Yang B, et al. Fourfold reduction of water permeability in inner medullary collecting duct of aquaporin-4 knockout mice. Am J Physiol. 1998,274(2Pt1): C549-54
[27] Nielsen S, Frokiaer J, marples D, et al.Aquaporins in the kidney: from molecules to medicine .Physiol Rev 2002;82(1):205
[28] Calamita G, Ferri D, Gena P,et al. The inner mitochondrial membrane has aquaporin-8 water channels and is highly permeable to water. J Biol Chem, 2005, 280:17149-17153
[29] Desagher S, Martinou JC. Mitochondria as the central control point of apoptosis/Trends Cell Biol, 2000, 10:369-377
[30] Kreda SM, Gynn MC , Fenstermacher DA, et al. Eqr-ession and localization of epithelial aquaorins in the odult human-lung. AM J Respir Cell Mol Biol ,2001 ,24 (3) :224-234.
[31] King LS ,Nielsen S ,Agre P. Aquaporins and the respiratory system: advice for a lung investigator. J Clin Invest ,2000 ,105 (1): 15-16.
[32] Wellner RN , Hoque ST, Goldsmith CM ,et al. Evidence that aquaporin-8 is located in the basolateral membrane if rat submandibular gland acinar cells . Pfugers Arch, 2000 ,441 :49-56.
[33] Elkjaer ML ,Nejsum LN , Gresz V , et al. Immunolocalization of aquaporin 8 in rat kidney, liver, testis , epidedymis, jeju-num ,colon, principal bronchi and salivary glands . Am J Physiol Renal Physiol, 2001 ,281 (6): 1047-1057.
[34] Song Y, J ayaraman S ,Yang B ,et al. Role of aquaporin water channels in airway fluid transport, humidification and surface liquid hydration. J Gen Physiol, 2003, 117:573-582
[35] Song Y, Ma T, Mathay MA ,et al. Role of aquaporin-4 in air-space-to-capollaru ater permeability in intact mouse lung measured by a novel gravimetric method. J Gen Physoil ,2000 ,155 (1): 17-27
[36] Bai C , Fukuda N, Song Y,et al. Lung fluid transort in aquapoein-1 and aquaporin-4 knockout mice . J Clin Invest ,1999 ,103 (4) :555-561
[37] Ma T ,Fukuda N ,Song Y,et al. Lung fluid t ransport in aquapoein-5 knockout mice . J Clin Invest ,2000 ,105 (1): 93-100
[38] King LS. Decreased pulmonary vascular permeability in aquaporin-1-null humans. Proc Natl Acad Sci ,2002 ,99 :1059-1063
[39] Umenishi F ,Cater P ,Yang B. Sharp increase in rat ling water channel expression in the perinaal period Am. J Respir Cell Mol Biol ,1996 ,15 :3 - 11
[40] Song Y,Verkman AS. Aquaporin-5 dependent fluid secretion in airway submucosal glands . J Biol Chem, 2001 ,276 :41288-41292
[41] Towne JE, Harrod Ks, Krane CM, et al. Decreased expression of AQP1 and AQP5 in mouse after acute viral infection. Am J respire Cell Mol Biol, 2000, 22:33-44
[42] Gabazza EC , Kasper M , Ohta K,et al. Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the mouse. Pathol Int ,2004 ,54 (10):774-780
[43] Tsang KW, Leung JC , Tipoe GL ,et al. Down-regulation of aquaporin 3 in bronchiectatic airways in vivo. Respir Med ,2003 ,97 (1): 59-64
[44] Saadoun S ,Verkman AS. Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature ,2005 ,434 :786-792
[45] Xiang Y, Ma B , Li T ,et al. Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis . Acta Pharmacol Sin ,2004 ,25 (6) :812-816
[46] Matsuzald T, TajikaY, Ablimit A, et al. Aquaporins in the digestive systerm . Med Electron Microsc, 2004.37(2):71-80
[47] Ma T ,Jayaraman S ,Wang KS,et al. Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels. Am J Physiol Cell Physiol,2001,280( 1 ):C 126-34
[48] Silbersldn C, Kjerbel A, Amodo G, et al. Functional characterization and Localization of AQP3 in the human colon. Braz J Med Biol Res, 1999, 32(10): 1303-1313
[49] Itoh A, Tsujikawa T, Fujiyama Y,et al. Enhancement of aquaporin-3 by vasoactive intestinal polypeptide in a human colonic epithelial cell line. Gastroenterol Hepatol.2003; 18(2):203 -10
[50] Wang KS ,Ma T ,Filiz F , et al. Colon water transport in transgenic mice lacking aquaporin-4 water channels . Am J Physiol Gastrointest Liver Physiol ,2000 ,279(2) :G463-470
[51] Krane CM, Melvin JE, Nguyen HV, et al. Salivary acinar cells from aquaporin 5 deficient mice have decreased membrane water permeability and altered cell volume regulation. J Biol Chem, 2001,276: 234313-2340
[52] Matsuki M,Hashimoto S ,Shimono M, et al. Involvement of aquaporin-5 water channel in osoregulation in parotid secretory granules. Membr Biol ,2005 , 203 (3) :119-126
[53] Yang B, Song Y, Zhao D,Verkman A S .Phenotype analysis of aquaporin-8 null mice. Am J Physiol Cell Physiol, 2005, [Epub ahead of print]
[54] Venero JL , Vizuete ML , Machado A , et al. Aquaporins in the central nervous system. Prog Neuro biol ,2001 ,63 (3) :321 - 336
[55] Longatti PL, Basaldella L, Orvieto E , et al. Choroid plexus and aquaporinl: a novel explanation of cerebrospinal fluid production. Pediatr Neurosurg ,2004 ,40 (6): 277
[56] Moon Y, Hong SJ , Shin D , et al. Increased aquaporinl expression in choroid plexus epithelium after systemic hyponatremia. Neuro sci Lett ,2006 ,395 (1) :1
[57] Solenov EL,Vetrivel L, Oshio K ,et al. Optical measurement of swelling and water transport in spinal cord slices from aquaporin null mice. J Neurosci Methods. 2002; 113:85-90
[58] Verkman A S. More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci, 2005; 118:3225-3232
[59] Saadoun S , Papadopoulos MC , Watanabe H, et al. Involvement of aquaporin4 in astroglial cell migration and glial scar formation[J ]. J Cell Sci ,2005 ,118 (24): 5691
[60] Hiroaki Y, Tani K, Kamegawa A, et al. Implications of the aquaporin4 structure on array formation and cell adhesion[J ]. J Mol Biol ,2006 ,355 (4) :628
[61] Papadopoulos MC, Manley GT, Krishna S ,et al .Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. Faseb J.2004;18:1291-1293
[62] Binder DK, Oshio K, Ma T, et al. Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport.2004;15 :259-262
[63] Da T, Verkman AS, Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia. Invest Ophthalmol Vis Sci. 2004;45 :4477-4483
[64] HuangD, ChenP ,ChenS, et al. Expression patterns of aquaporins in the inner ear: evidence for concerted actions of multiple types of aquaporins to facilitate water transport in the cochlea. Hear Res.2002;165:85-95
[65] Nagelhus EA, Mathiisen TM, Ottersen OP, et al. Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience.2004; 129:905-913
[66] Verman AS. Role of aquaporin water channels in eye function. Exp Eye Res. 2003,76:137-143
[67] Berry V, Francis P, Kaushal S, et al. Missense underlie autosomal dominant 'polymorphic'and lamellar cataracts linked tol2q[J]. Nat Genet, 2000, 25(1):15-7
[68] Hasegawa H, Lian SC, Finkbeiner WE, et al. Extra renal tissue distribution of CHIP28 water channels by in situ hybridization and antibody staining[J]. Am J Physiol, 1994,266(4):C893-903
[69] Frigeri A, Cropper MA, Turck CW, et al. Immunolocalization of the mercurial- Insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes. Proc Natl Acad sci USA, 1995, 92(10):4328-31
[70] Thiagarajah JR, Verkman AS. Aquaporin deletion in mice reduces corneal water permeability and delays restoration of transparency after swelling. J Biol Chem, 2002,277(21):19139-4
[71] Varadaraj K, Kumari S, Shiels A, et al. Regulation of aquaporin water permeability in the lens. lnvest Ophthalmol Vis Sci, 2005, 46(4): 1393-402
[72] Levin MH, Verkman AS. Aquaporin-dependent water permeation at the mouse ocular surface: in vivo microfiuorimetric measurements in cornea and conjunctiva. Invest Ophthalmol Vis Sci, 2004, 45(12):4423-32
[73] Iandiev I, Pannicke T, Reichel MB, et al. Expression of aquaporin-1 immunoreactivity by photoreceptor cells in the mouse retina .Neurosci Lett, 2005, 388(2):96-99
[74] Yang H, Reinach PS, Koniarek JP, et al. Fluid transport by cultured corneal epithelial celll layers[J]. Br J Ophthalmol, 2000, 84(2):199-204
[75] Patil RV, Han Z, Yiming M, et al. Fluid transport by human nonpigmented ciliary epithelial layers in culture: a homeostatic role for aquaporin-1. Am J Physiol Cell Physiol, 2001, 281(4): C1139-45
[76] Ohashi Y, Ishida R, Kojlma T, et al. Abnormal protein profiles in tears with dry eye syndrome.Am J Ophthalmol, 2003, 136(2):291-299
[77] Zhang D, Vetrivel L, Verkman AS. Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production. J Gen Physiol, 2002,1999(6): 561-569
[78] Sougrat R, Morand M, Gondran C, et al. Functional expression of AQP3 in human skin epidermis and reconstructed epidermis. J Invest Dermatol. 2002; 118:678-685
[79] Ma T, Hara M, Sougrat T, et al. Impaired stratum corneum hydration in mice lacking epidermal water channel aquaporin-3. J Biol Chem. 2002;277:17147-17153.
[80] Hara M, Verkman AS. Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Proc Natl Acad Sci USA. 2003;100:7360-7365.
[81] Marc Dumas, Neil S. Sadick, Emmanuelle Noblesse, et al. Hydrating skin by stimulating biosynthesis of aquaporins. J Drugs Dermatol. 2007 Jun;6(6 Suppl): s20-4
[82] Cong CAO, Yun SUN, Sarah HEALEY, et al. EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. Biochem. J. 2006 , 400:225-234
[83] Mariko H C, Verkman A S. Aquaporin-3 facilitates epidermal cell migration and proliferation during wound healing. J Mol Med. 2008 Feb;86(2):221-31
[84] Olsson M, Broberg A, Jernas M, et al. Increased expression of aquaporin 3 in atopic eczema. Allergy. 2006 Sep;61(9):l 132-7
[85] Boury-Jamot M, Sougrat R, Tailhardat M, et al. Expression and function of aquaporins in human skin is aquaporine-3: Is aquaporin-3 just a glycerol transporter? Biochim Biophys Acta. 2006;1758:1034-1042.
[86] Bellemere G, Von Stetten O, Oddos T. Retinoic acid increases aquaporin 3 expression in normal human skin. J Invest Dermatol. 2008 Mar;128(3):542-8.
[87] Cao C, Wan S, Jiang Q, et al. All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. J Cell Physiol. 2008 May;215(2):506-16
[1]Goihman-Yahr M.Skin aging and photoaging:an outlook.Clin Dermatol.1996Mar-Apr;14(2):153-60.
[2]Anthony V,Benedetto,DO.The environment and skin aging.Clin in Derm,1998,16(1):129-139.
[3]Gilchrest B A,Szabo G,Flynn E.Chronologic and Actinically induced aging in human facial skin.J Invest Derm,1983,80(suppl 1):81-85
[4]Chung J H.Photoaging in Asians.Photodermtol photoimmunol photomed,2003,19(3):109-121
[5]Bernstein EF,Uitto J.The effect of photoaging on dermal extracellular matrix.Clin Dermatol,1996,14(2):143-151
[6]Ei-Domyati M,Attia S,Saleh F,et al.Intrinsic aging vs.photoaging:a comparative histopathological,immnohistochemical,and ultrastructural study of skin.Exp Dermtol,2002,11(5):398-405.
[7]KangS,F isherG J,V oorheesJJ,et al.Photoaging and topical tretinoin.Ar chD ermatol,1997,13 3:1280-1284
[8]Gilchrest BA.A review of skin aging and its medical therapy.Br JDe rmatol,1996,135:8 67-875
[9]DeBuys HV,Levy SB,Murray JC,et al.Modern approaches to photoprotection.Dermatol Clin,2000,18(4):577
[10]Humbert P.Topical vitamin C in the treatment of photoaged skin.Eur Derrnatol.2001 Mar-Apr;11(2):172-3.Review
[11]Lin JY,Selim MA,Shea CR,et al.UV photoprotection by combination topical antioxidants vitamin C and vitamin E.J Am Acad Dermatol,2003,48:866-874
[12]Thiele JJ,Traber MG.Packer L.Depletion of human stratum corneum vitamin E:an early and sensitive in vivo marker of UV induced photo-oxidation.J Invest Dermatol.1998 May;110(5):756-61.
[13]Ritter EF.Axelrod M.Minn KW,et al.Modulation of ultraviolet light-induced epidermal damage:beneficial effects oftocopherol.Plast Reconstr Surg.1997 Sep;100(4):973-80
[14]Riceiarelli R,Maroni P,Ozer N,et al.Age—dependent increase of collagenase expression can be reduced by alpha—tecopherol via proteinkinase C inhibition.Free Radic Biol Med,1999,27(7—8):729—737
[15]StaIL W.siesH.Carotenoids and protection against solar UV radiation[J].Skin Pharmacol Appl skin Physiol,2002,15(5):291
[16]Hoppe U,Bergemann J,DiembeckW,et al.Coenzyme Q10,a cutaneous antioxidant and energizer.Biofactom,1999,9(2—4):371-378.
[17]梁建梅.皮肤光老化的外用药物治疗.现代中西医结合杂志,2005,14(19):1193
[18]Mckenzie RC.Selenium,ultraviolet radiation and the skin.Clin ExpDermatol.2000,25(8):631.
[19]Tsukahara K,Moriwaki S,Hotta M,et al.The effect of sunscreen on skin elastase activity induced by ultraviolet-A irradiation.Biol Pharm Bull.2005Dec;28(12):2302-7
[20]陈昆,常宝珠,郑家润,等.抗氧化剂与紫外线相关性皮肤病.国外医学皮肤性病分册:2003,29(6):349-351
[21]Mitani H,Koshiishi I,Sumita T,et al.Prevention of the photodamage in the hairless mouse dorsal skin by kojic acid as an iron chelator.Eur J Pharmacol,2001,411:169-174
[22]Xia J,Song X,Bi Z,Chu W,Wan Y.UV-induced NF-kappaB activation and expression of IL-6 is attenuated by(-)-epigallocatechin-3-gallate in cultured human keratinocytes in vitro.Int J Mol Med.2005 Nov;16(5):943-50
[23]Meeran SM,Mantena SK,Katiyar SK.Prevention of ultraviolet radiation-induced immunosuppression by(-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair.Clin Cancer Res.2006 Apr 1;12(7 Pt 1):2272-80
[24]Luo D,Min W,Lin XF,Wu D,Xu Y,Miao X.Effect of epigallocatechingallate on ultraviolet B-induced photo-damage in keratinocyte Cell line.Am J Chin Med.2006;34(5):911-22
[25]姚煜,田涛,南克俊.白藜芦醇抗衰老免疫机制的研究.中药材,2006.29(5):464-466
[26]Kang S,Cho S,Chung JH,Hammerberg C,etal..Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo.Am J Pathol.2005 Jun;166(6):1691-9
[27]雷小兵,等.全反式维A酸对UVA诱导人成纤维细胞胶原合成的影响.中国皮肤性病学杂志,2004,18(4):202
[28]Lowe N,Gifford M,Tanghetti E,et al.Tazarotene 0.1%cream versus tretinoin 0.05%emollient cream in the treatment of photodamaged facial skin:a multicenter,double-blind,randomized,parallel group study.J Cosmet Laser Ther,2004,6:79-85
[29]Kang S,Leyden JJ,Lowe NJ,et al.Tazarotene cream for the treatment of facial photodamage:a multicenter,investigator-masked,randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks. Arch Dermatol, 2001,137: 1597-1604
[30] Hoick DE, Ng JD.Facial skin rejuvenation. Curr Opin Ophthalmol. 2003 Oct; 14(5):246-52. Review.
[31] Goldman MP, Marchell N, Fitzpatrick RE. Laser skin resurfacing of the face with a combined CO2/Er:YAG laser. Dermatol Surg. 2000 Feb;26(2): 102-4
[32] Rostan EF, Fitzpatrick RE, Goldman MP. Laser resurfacing with a long pulse erbium: YAG laser compared to the 950 ms pulsed CO(2) laser. Lasers Surg Med. 2001 ;29(2): 136-41
[33] YAGHMAI D , GARDEN J M , BAKUS A D , et al. Comparison of a 1064 nm laser and a 1320 nm laser for the nonablative treatment of acne scars. Dermatol Surg, 2005 ,31 (8 Pt 1)-.903-909
[34] BITTER P H. Noninvasive rejuvenation of photodamaged skin using serial, full - face intense pulsed light treatments. Dermatol Surg, 2000 ,26(9) :835 -842
[35] WEISS R A, WEISS M A, BEASL EY K L. Rejuvenation of photoaged skin : 5 years results with intense pulsed light of the face , neck , and chest. Dermatol Surg, 2002 ,28 (12) :1115-1119
[36] SADICK N S , WEISS R, KILMER S , BITTER P. Photorejuvenation with intense pulsed light: results of a multi - center study. J Drugs Dermatol, 2004 ,3(1): 41-49
[37] WEISS R A, WEISS M A, MUNAVALL I G, et al. Monopolar radiofrequency facial tightening : a retrospective analysis of efficacy and safety in over 600 treatments. J Drugs Dermatol, 2006 ,5 (8) :707 - 712
[38] RUSSELL B A, KELL ETT N , REILL Y L R. A study to determine the efficacy of combination L ED light therapy (633 nm and 830 nm) in facial skin rejuvenation. J Cosmet Laser Ther, 2005 ,7 (3-4) :196 - 200
[39] Hernandez-Perez E, Ibiett EV Gross and microscopic findings in patients undergoing microdermabrasion for facial rejuvenation Dermatol Surg. 2001 Jul;27(7):637-40
[40] Spencer JM Microdermabrasion. Am J Clin Dermatol.2005;6(2):89-92
[41] Briden ME. Alpha-hydroxyacid chemical peeling agents: case studies and rationale for safe and effective use Cutis. 2004 Feb;73(2 Suppl): 18-24
[42]Zakopoulou N,Kontochristopoulos G..Superficial chemical peels.J Cosmet Dermatol.2006 Sep;5(3):246-53
[43]Fagien S,Klein AW.A brief overview and history of temporary fillers:evolution,advantages,and limitations.Plast Reconstr Surg.2007;120(6 Suppl):8S-16S
[44]Dastoor SF,Misch CE,Wang HL.Dermal fillers for facial soft tissue augmentation.J Oral Implantol.2007;33(4):191-204
[45]Beer K,Waibel J.Botulinum toxin type A enhances the outcome of fractional resurfacing of the cheek.J Drugs Dermatol.2007;6(11):1151-2
[46]Kaplan SE,Sherris DA,Gassner HG,et al.The use of botulinurn toxin A in perioral rejuvenation.Facial Plast Surg Clin North Am.2007;15(4):415-21,ⅴ-ⅵ