通过分子生物学、组织学及临床检测手段对比研究视黄醇和视黄酸作用在人体皮肤上的功效
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- 英文论文题名：A comparative study of the effects of retinol and retinoic acid on histological,molecular,and clinical properties of human skin
- 论文作者：Rong Kong ; Yilei Cui ; Gary J.Fisher ; 王小娟 ; 陈银杯 ; Louise M. Schneider ; Gopa Majmudar ; 廖峰
- 英文论文作者：Rong Kong ; Yilei Cui ; Gary J. Fisher ; Xiaojuan Wang ; Yinbei Chen ; Louise M. Schneider ; Gopa Majmudar ; Feng Liao ; LResearch and Development ; Amway Corporation ; Department of Dermatology ; University of Michigan ; Amway (China) Research and Development Centre
- 年：2016
- 作者机构：安利公司;密歇根州大学皮肤病学部;安利(中国)研发中心有限公司;
- 论文关键词：视黄醇 ; 视黄酸 ; 表皮厚度 ; 胶原蛋白 ; 祛皱 ; 体内共焦显微镜
- 英文论文关键词：Retinol ; Retinoic acid ; Epidermal thickness ; Collagen ; Wrinkle reduction ; In vivo Confocal microscopy
- 会议召开时间：2016-06-15
- 会议录名称：第十一届中国化妆品学术研讨会论文集
- 英文会议录名称：The Proceedings of the 11th Seminar on Cosmetic China
- 语种：中文
- 分类号：TQ658.2
- 学会代码：ZGXE
- 会议名称：第十一届中国化妆品学术研讨会
- 会议地点：中国上海
- 主办单位：中国香料香精化妆品工业协会
- 学会名称：中国香料香精化妆品工业协会
- 页数：10
- 文件大小：1295k
- 原文格式：O
- 会议级别：全国
摘要
目的:全反式视黄醇是视黄酸的前体,且是有效的抗衰老成分,被广泛应用于皮肤护理产品中。相比之下,视黄酸通常被认为具有更好的抗衰老效果,但关于直接对比视黄醇和视黄酸对皮肤功效的研究非常有限。通过研究,对比视黄醇和视黄酸对皮肤结构,以及与皮肤功能相关的基因和蛋白质表达的影响。此外,检测视黄醇治疗对皮肤外观的作用效果。方法:通过HE染色和体内共焦显微镜进行皮肤组织学检查。此外,通过RT-PCR与免疫组化的方法分析皮肤基因与蛋白的表达水平。视黄醇改善皮肤外观效果评估是使用基于皱纹分析的图像分析方法进行的。结果:通过4周的视黄醇和视黄酸的使用,表皮厚度增加,真皮内胶原蛋白基因1型(COL1A1)和3型(COL3A1)以及他们对应的Ⅰ型、Ⅲ型前胶原蛋白表达都得到增加。同时,面部图像分析显示使用视黄醇12周后,面部皱纹呈现显著下降。结论:研究结果表明,如皮肤活检和无创图像分析所示,局部应用视黄醇可显著影响到表皮与真皮的细胞分子特性。虽然幅度相对较小,但视黄醇也如同视黄酸一样表达出类似的皮肤组织学以及基因和蛋白质表达的变化。
Objectives:All-trans retinol,a precursor of retinoic acid,is an effective anti-aging treatment widely used in skin care products.In comparison,topical retinoic acid is believed to provide even greater anti-aging effects;however,there is limited research directly comparing the effects of retinol and retinoic acid on skin.In this study,we compare the effects of retinol and retinoic acid on skin structure and expression of skin function-related genes and proteins.We also examine the effect of retinol treatment on skin appearance.Methods:Skin histology was examined by H&E staining and in vivo confocal microscopy.Expression levels of skin genes and proteins were analyzed using RT-PCR and immunohistochemistry.The efficacy of a retinol formulation in improving skin appearance was assessed using digital image-based wrinkle analysis.Results:Four weeks of retinoic acid and retinol treatments both increased epidermal thickness,and upregulated genes for collagen type 1(COL1A1),and collagen type 3(COL3A1) with corresponding increases in procollagen Ⅰ and procollagen Ⅲ protein expression.Facial image analysis showed a significant reduction in facial wrinkles following 12 weeks of retinol application.Conclusions:The results of this study demonstrate that topical application of retinol significantly affects both cellular and molecular properties of the epidermis and dermis,as shown by skin biopsy and noninvasive imaging analyses.Although the magnitude tends to be smaller,retinol induces similar changes in skin histology,and gene and protein expression as compared to retinoic acid application.These results were confirmed by the significant facial anti-aging effect observed in the retinol efficacy clinical study.
Objectives:All-trans retinol,a precursor of retinoic acid,is an effective anti-aging treatment widely used in skin care products.In comparison,topical retinoic acid is believed to provide even greater anti-aging effects;however,there is limited research directly comparing the effects of retinol and retinoic acid on skin.In this study,we compare the effects of retinol and retinoic acid on skin structure and expression of skin function-related genes and proteins.We also examine the effect of retinol treatment on skin appearance.Methods:Skin histology was examined by H&E staining and in vivo confocal microscopy.Expression levels of skin genes and proteins were analyzed using RT-PCR and immunohistochemistry.The efficacy of a retinol formulation in improving skin appearance was assessed using digital image-based wrinkle analysis.Results:Four weeks of retinoic acid and retinol treatments both increased epidermal thickness,and upregulated genes for collagen type 1(COL1A1),and collagen type 3(COL3A1) with corresponding increases in procollagen Ⅰ and procollagen Ⅲ protein expression.Facial image analysis showed a significant reduction in facial wrinkles following 12 weeks of retinol application.Conclusions:The results of this study demonstrate that topical application of retinol significantly affects both cellular and molecular properties of the epidermis and dermis,as shown by skin biopsy and noninvasive imaging analyses.Although the magnitude tends to be smaller,retinol induces similar changes in skin histology,and gene and protein expression as compared to retinoic acid application.These results were confirmed by the significant facial anti-aging effect observed in the retinol efficacy clinical study.
引文
[1]Kligman LH,Duo CH,Kligman AM.Topical retinoic acid enhances the repair of ultraviolet damaged dermal connective tissue.Connect Tissu Res[J]1984;12:139-50.
[2]Kligman AM,Grove GL,Hirose R et al.Topical tretinoin for photoaged skin.J Am Acad Dermatol[J]1986;15:836-59.
[3]Griffiths C,Russman AN,Majmudar G et al.Restoration of collagen formation in photodamaged human skin by tretinoin(retinoic acid).New Engl J Med[J]1993;329:530-5.
[4]Fisher GJ,Reddy AP,Datta SC et al.All-trans retinoic acid induces cellular retinol-binding protein in human skin in vivo.J Investig Dermatol[J]1995;105:80-6.
[5]Fisher GJ,Datta SC,Talwar HS et al.Molecular basis of sun-induced premature skin ageing and retinoid antagonism.Nature[J]1996;379:335-9.
[6]Mukherjee S,Date A,Patravale V et al.Retinoids in the treatment of skin aging:an overview of clinical efficacy and safety.Clin Interv Aging[J]2006;1:327-48.
[7]Oda R,Shimizu R,Sabatine S et al.Effects of structural changes on retinoid cytotoxicity in the CHO clonal assay.In Vitro Toxicol[J]1996;9:173-81.
[8]Kang S,Duell EA,Fisher GJ et al.Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation.J Investig Dermatol[J]1995;105:549-56.
[9]Fluhr J,Vienne M-P,Lauze C et al.Tolerance profile of retinol,retinaldehyde and retinoic acid under maximized and long term clinical conditions.Dermatology[J]1999;199:57-60.
[10]Fisher GJ,Wang Z,Datta SC et al.Pathophysiology of premature skin aging induced by ultraviolet light.New Engl J Med[J]1997;337:1419-29.
[11]Pierard-Franchimont C,Castelli D,CromphautⅣet al.Tensile properties and contours of aging facial skin.A controlled double-blind comparative study of the effects of retinol,melibiose-lactose and their association.Skin Res Technol[J]1998;4:237-43.
[12]Varani J,Warner RL,Gharaee-Kermani M et al.VitaminA antagonizes decreased cell growth and elevated collagen degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin1.J Investig Dermatol[J]2000;114:480-6.
[13]Duell EA,Derguini F,Kang S et al.Extraction of human epidermis treated with retinol yields retro-retinoids in addition to free retinol and retinyl esters.J Investig Dermatol[J]1996;107:178-82.
[14]Kurlandsky SB,Xiao J-H,Duell EA et al.Biological activity of all-trans retinol requires metabolic conversion to all-trans retinoic acid and is mediated through activation of nuclear retinoid receptors in human keratinocytes.J Biol Chem[J]1994;269:32821-7.
[15]Qu D,Park Y.Skin youthfulness index-a novel model correlating age with objectively measured visual parameters of facial skin.IFSCC Magazine[J]2014;17:8-16.
[16]Quan T,Wang F,Shao Y et al.Enhancing structural support of the dermal microenvironmentactivates fibroblasts,endothelial cells,and keratinocytes in aged human skin in vivo.J Investig Dermatol[J]2013;133:658-67.
[17]Corcuff P,Bertrand C,Leveque JL.Morphometry of human epidermis in vivo by real-time confocal microscopy.Arch Dermatol Res[J]1993;285:475-81.
[18]Huzaira M,Rius F,Rajadhyaksha M et al.Topographic variations in normal skin,as viewed by in vivo reflectance confocal microscopy.J Invest Dermatol[J]2001;116:846-52.
[19]Nouveau-Richard S,Monot M,Bastien P et al.In vivo epidermal thickness measurement:ultrasound vs.confocal imaging.Skin Res Technol[J]2004;10:136-40.
[20]Kolbe L,Kligman AM,Schreiner V et al.Corticosteroidinduced atrophy and barrier impairment measured by non-invasive methods in human skin.Skin Res Technol[J]2001;7:73-7.
[21]Rajadhyaksha M,Grossman M,Esterowitz D et al.In vivo confocal scanning laser microscopy of human skin:melanin provides strong contrast.J Investig Dermatol[J]1995;104:946-52.
[22]Rajadhyaksha M,Gonzalez S,Zavislan JM et al.In vivo confocal scanning laser microscopy of human skinⅡ:advances in instrumentation and comparison with histology1.J Investig Dermatol[J]1999;113:293-303.
[23]Lavker RM,Zheng P,Dong G.Aged skin:a study by light,transmission electron,and scanning electron microscopy.J Investig Dermatol[J]1987;88:44-51.
[24]Yaar M,Gilchrest BA.Aging of skin.In:BT Fitzpatrick,IM Freedberg,AZ Eisen,eds.Aging of skin.New York,NY:McGraw Hill[J],1999:pp.1697.
[25]Kligman AM,Dogadkina D,Lavker RM.Effects of topical tretinoin on non-sun-exposed protected skin of the elderly.J Am Acad Dermatol[J]1993;29:25-33.
[26]El-Domyati M,Attia S,Saleh F et al.Intrinsic aging vs.photoaging:a comparative histopathological,immunohistochemical,and ultrastructural study of skin.Exp Dermatol[J]2002;11:398-405.
[27]Fenske NA,Lober CW.Structural and functional changes of normal aging skin.J Am Acad Dermatol[J]1986;15:571-85.
[28]Fisher GJ,Kang S,Varani J et al.Mechanisms of photoaging and chronological skin aging.Arch Dermatol[J]2002;138:1462-70.
[29]Kambayashi H,Yamashita M,Odake Y et al.Epidermal changes caused by chronic low-dose UV irradiation induce wrinkle formation in hairless mouse.J Dermatol Sci[J]2001;27:19-25.
[30]Chen S,Kiss I,Tramposch KM.Effects of all-trans retinoic acid on UVB-Irradiated and non-irradiated hairless mouse skin.J Investig Dermatol[J]1992;98:248-54.
[31]Kang S.Photoaging and tretinoin.Dermatol Clin[J]1998;16:357-64.
[32]Kang S,Fisher GJ,Voorhees JJ.Photoaging and topical tretinoin:therapy,pathogenesis,and prevention.Arch Dermatol[J]1997;133:1280-4.
[33]Talwar HS,Griffiths CE,Fisher GJ et al.Reduced typeⅠand typeⅢprocollagens in photodamaged adult human skin.J Investig Dermatol[J]1995;105:285-90.
[34]Bouloc A,Vergnanini AL,Issa MC.A double-blind randomized study comparing the association of Retinol and LR2412 with tretinoin 0.025%in photoaged skin.J Cosmet Dermatol[J]2015;14:40-6.
[35]Wielowieyska-Szybinska D,Bialek-Galas K,Podolec K et al.The use of reflectance confocal microscopy for examination of benign and malignant skin tumors.Postepy Dermatol Alergol[J]2014;31:380.
[36]Ulrich M,Lange-Asschenfeldt S.In vivo confocal microscopy in dermatology:from research to clinical application.J Biomed Opt[J]2013;18:061212-12.
[37]Smith L,MacNeil S.State of the art in non-invasive imaging of cutaneousmelanoma.Skin Res Technol[J]2011;17:257-69.
[2]Kligman AM,Grove GL,Hirose R et al.Topical tretinoin for photoaged skin.J Am Acad Dermatol[J]1986;15:836-59.
[3]Griffiths C,Russman AN,Majmudar G et al.Restoration of collagen formation in photodamaged human skin by tretinoin(retinoic acid).New Engl J Med[J]1993;329:530-5.
[4]Fisher GJ,Reddy AP,Datta SC et al.All-trans retinoic acid induces cellular retinol-binding protein in human skin in vivo.J Investig Dermatol[J]1995;105:80-6.
[5]Fisher GJ,Datta SC,Talwar HS et al.Molecular basis of sun-induced premature skin ageing and retinoid antagonism.Nature[J]1996;379:335-9.
[6]Mukherjee S,Date A,Patravale V et al.Retinoids in the treatment of skin aging:an overview of clinical efficacy and safety.Clin Interv Aging[J]2006;1:327-48.
[7]Oda R,Shimizu R,Sabatine S et al.Effects of structural changes on retinoid cytotoxicity in the CHO clonal assay.In Vitro Toxicol[J]1996;9:173-81.
[8]Kang S,Duell EA,Fisher GJ et al.Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation.J Investig Dermatol[J]1995;105:549-56.
[9]Fluhr J,Vienne M-P,Lauze C et al.Tolerance profile of retinol,retinaldehyde and retinoic acid under maximized and long term clinical conditions.Dermatology[J]1999;199:57-60.
[10]Fisher GJ,Wang Z,Datta SC et al.Pathophysiology of premature skin aging induced by ultraviolet light.New Engl J Med[J]1997;337:1419-29.
[11]Pierard-Franchimont C,Castelli D,CromphautⅣet al.Tensile properties and contours of aging facial skin.A controlled double-blind comparative study of the effects of retinol,melibiose-lactose and their association.Skin Res Technol[J]1998;4:237-43.
[12]Varani J,Warner RL,Gharaee-Kermani M et al.VitaminA antagonizes decreased cell growth and elevated collagen degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin1.J Investig Dermatol[J]2000;114:480-6.
[13]Duell EA,Derguini F,Kang S et al.Extraction of human epidermis treated with retinol yields retro-retinoids in addition to free retinol and retinyl esters.J Investig Dermatol[J]1996;107:178-82.
[14]Kurlandsky SB,Xiao J-H,Duell EA et al.Biological activity of all-trans retinol requires metabolic conversion to all-trans retinoic acid and is mediated through activation of nuclear retinoid receptors in human keratinocytes.J Biol Chem[J]1994;269:32821-7.
[15]Qu D,Park Y.Skin youthfulness index-a novel model correlating age with objectively measured visual parameters of facial skin.IFSCC Magazine[J]2014;17:8-16.
[16]Quan T,Wang F,Shao Y et al.Enhancing structural support of the dermal microenvironmentactivates fibroblasts,endothelial cells,and keratinocytes in aged human skin in vivo.J Investig Dermatol[J]2013;133:658-67.
[17]Corcuff P,Bertrand C,Leveque JL.Morphometry of human epidermis in vivo by real-time confocal microscopy.Arch Dermatol Res[J]1993;285:475-81.
[18]Huzaira M,Rius F,Rajadhyaksha M et al.Topographic variations in normal skin,as viewed by in vivo reflectance confocal microscopy.J Invest Dermatol[J]2001;116:846-52.
[19]Nouveau-Richard S,Monot M,Bastien P et al.In vivo epidermal thickness measurement:ultrasound vs.confocal imaging.Skin Res Technol[J]2004;10:136-40.
[20]Kolbe L,Kligman AM,Schreiner V et al.Corticosteroidinduced atrophy and barrier impairment measured by non-invasive methods in human skin.Skin Res Technol[J]2001;7:73-7.
[21]Rajadhyaksha M,Grossman M,Esterowitz D et al.In vivo confocal scanning laser microscopy of human skin:melanin provides strong contrast.J Investig Dermatol[J]1995;104:946-52.
[22]Rajadhyaksha M,Gonzalez S,Zavislan JM et al.In vivo confocal scanning laser microscopy of human skinⅡ:advances in instrumentation and comparison with histology1.J Investig Dermatol[J]1999;113:293-303.
[23]Lavker RM,Zheng P,Dong G.Aged skin:a study by light,transmission electron,and scanning electron microscopy.J Investig Dermatol[J]1987;88:44-51.
[24]Yaar M,Gilchrest BA.Aging of skin.In:BT Fitzpatrick,IM Freedberg,AZ Eisen,eds.Aging of skin.New York,NY:McGraw Hill[J],1999:pp.1697.
[25]Kligman AM,Dogadkina D,Lavker RM.Effects of topical tretinoin on non-sun-exposed protected skin of the elderly.J Am Acad Dermatol[J]1993;29:25-33.
[26]El-Domyati M,Attia S,Saleh F et al.Intrinsic aging vs.photoaging:a comparative histopathological,immunohistochemical,and ultrastructural study of skin.Exp Dermatol[J]2002;11:398-405.
[27]Fenske NA,Lober CW.Structural and functional changes of normal aging skin.J Am Acad Dermatol[J]1986;15:571-85.
[28]Fisher GJ,Kang S,Varani J et al.Mechanisms of photoaging and chronological skin aging.Arch Dermatol[J]2002;138:1462-70.
[29]Kambayashi H,Yamashita M,Odake Y et al.Epidermal changes caused by chronic low-dose UV irradiation induce wrinkle formation in hairless mouse.J Dermatol Sci[J]2001;27:19-25.
[30]Chen S,Kiss I,Tramposch KM.Effects of all-trans retinoic acid on UVB-Irradiated and non-irradiated hairless mouse skin.J Investig Dermatol[J]1992;98:248-54.
[31]Kang S.Photoaging and tretinoin.Dermatol Clin[J]1998;16:357-64.
[32]Kang S,Fisher GJ,Voorhees JJ.Photoaging and topical tretinoin:therapy,pathogenesis,and prevention.Arch Dermatol[J]1997;133:1280-4.
[33]Talwar HS,Griffiths CE,Fisher GJ et al.Reduced typeⅠand typeⅢprocollagens in photodamaged adult human skin.J Investig Dermatol[J]1995;105:285-90.
[34]Bouloc A,Vergnanini AL,Issa MC.A double-blind randomized study comparing the association of Retinol and LR2412 with tretinoin 0.025%in photoaged skin.J Cosmet Dermatol[J]2015;14:40-6.
[35]Wielowieyska-Szybinska D,Bialek-Galas K,Podolec K et al.The use of reflectance confocal microscopy for examination of benign and malignant skin tumors.Postepy Dermatol Alergol[J]2014;31:380.
[36]Ulrich M,Lange-Asschenfeldt S.In vivo confocal microscopy in dermatology:from research to clinical application.J Biomed Opt[J]2013;18:061212-12.
[37]Smith L,MacNeil S.State of the art in non-invasive imaging of cutaneousmelanoma.Skin Res Technol[J]2011;17:257-69.
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