寻常型银屑病皮损表皮Dsg1mRNA的表达
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摘要
背景:银屑病是以表皮过度增殖为主要发病特征的慢性复发性炎症性皮肤病,其根本发病机制尚未完全阐明。一般认为自身反应性T细胞介导的免疫反应为其主要发生机制,而近年来大量国内外研究已证明凋亡在银屑病发病中起着很重要的作用,其特征性的病理改变不仅与角质形成细胞(KC)异常增殖有关,也与KC凋亡异常有关。银屑病表皮角质形成细胞凋亡异常,许多凋亡相关分子的异常表达与其有关。
目的:通过检测银屑病与正常人表皮桥粒芯糖蛋白1(Dsg1)的表达,进一步探讨Dsg1在银屑病皮损角质形成细胞凋亡中的作用。
方法:采集34例皮肤标本(寻常型银屑病与正常人各17例),用中性蛋白酶分离真表皮,采用逆转录聚合酶链反应(RT-PCR)方法检测寻常型银屑病患者和正常人表皮细胞天冬氨酸特异性半胱氨酸蛋白酶3(caspase-3)与Dsg1mRNA的表达。
结果:(1)寻常型银屑病皮损表皮Dsg1mRNA的表达明显高于正常人(0.74±0.12～0.54±0.10)(P<0.05);(2) caspase-3 mRNA在两者间的表达无统计学意义(0.36±0.08～0.39±0.08)(P>0.05)。
结论:银屑病患者皮损表皮角质形成细胞的凋亡异常可能与Dsg1的异常表达有关。
Background:Psoriasis is a chronic, recurrent inflammatory skin disease characterized by epidermal hyperproliferation. The underlying pathogenic mechanism is still not completely clarified. Self-active T cell-mediated immune response is thoughted to be the main pathological mechanism of psoriasis.However,in recent years numerous studies have demonstrated that apoptosis plays a key role in the pathogenesis of psoriasis and that aberrant expression of many apoptosis-related molecules is related to be abnormal apoptosis of psoriatic keratinocytes.
Objective:To explore the action of desmoglein 1(Dsg1)in apoptosis of lesional psoriatic keratinocytes by examining the expression of dsg1 in the psoriatic and the normal epidermis.
Methods:A total of 34 skin samples (Biopsies of 17 patients with psoriasis vulgaris and 17 normal skin) were treated by dispase for separating intact epidermis from the dermis.Then the expressions of Dsg1 and caspase-3 in the epidemis were examined by RT-PCR.
Results:The psoriatic epidermis showed higher expression of dsg1 mRNA when compared to normal epidemis (0.74±0.12～0.54±0.10) (P < 0.05). There was no significant difference at caspase-3 mRNA level between the psoriatic and the normal epidermis(0.36±0.08～0.39±0.08) (P > 0.05)
Conclusion:The results of the study suggested that abnomal apoptosis process of psoriatic epidermal keratinocytes might be related to the aberrant expression of Dsg1.
目的:通过检测银屑病与正常人表皮桥粒芯糖蛋白1(Dsg1)的表达,进一步探讨Dsg1在银屑病皮损角质形成细胞凋亡中的作用。
方法:采集34例皮肤标本(寻常型银屑病与正常人各17例),用中性蛋白酶分离真表皮,采用逆转录聚合酶链反应(RT-PCR)方法检测寻常型银屑病患者和正常人表皮细胞天冬氨酸特异性半胱氨酸蛋白酶3(caspase-3)与Dsg1mRNA的表达。
结果:(1)寻常型银屑病皮损表皮Dsg1mRNA的表达明显高于正常人(0.74±0.12～0.54±0.10)(P<0.05);(2) caspase-3 mRNA在两者间的表达无统计学意义(0.36±0.08～0.39±0.08)(P>0.05)。
结论:银屑病患者皮损表皮角质形成细胞的凋亡异常可能与Dsg1的异常表达有关。
Background:Psoriasis is a chronic, recurrent inflammatory skin disease characterized by epidermal hyperproliferation. The underlying pathogenic mechanism is still not completely clarified. Self-active T cell-mediated immune response is thoughted to be the main pathological mechanism of psoriasis.However,in recent years numerous studies have demonstrated that apoptosis plays a key role in the pathogenesis of psoriasis and that aberrant expression of many apoptosis-related molecules is related to be abnormal apoptosis of psoriatic keratinocytes.
Objective:To explore the action of desmoglein 1(Dsg1)in apoptosis of lesional psoriatic keratinocytes by examining the expression of dsg1 in the psoriatic and the normal epidermis.
Methods:A total of 34 skin samples (Biopsies of 17 patients with psoriasis vulgaris and 17 normal skin) were treated by dispase for separating intact epidermis from the dermis.Then the expressions of Dsg1 and caspase-3 in the epidemis were examined by RT-PCR.
Results:The psoriatic epidermis showed higher expression of dsg1 mRNA when compared to normal epidemis (0.74±0.12～0.54±0.10) (P < 0.05). There was no significant difference at caspase-3 mRNA level between the psoriatic and the normal epidermis(0.36±0.08～0.39±0.08) (P > 0.05)
Conclusion:The results of the study suggested that abnomal apoptosis process of psoriatic epidermal keratinocytes might be related to the aberrant expression of Dsg1.
引文
[1]张正中,张学军,杨森,等.银屑病与细胞凋亡.国际皮肤性病学杂志,2006,(03).
[2]高奎斌,李萍,王雅坤,等.寻常性银屑病患者皮损中Caspase-3和bcl-xL的表达.中华皮肤科杂志,2004,(10).
[3] Dusek RL , Getsios S, Chen F. The Differentiation-dependent Desmosomal Cadherin Desmoglein 1 Is a Novel Caspase-3 Target That Regulates Apoptosis in Keratinocytes. J. Biol. Chem, 2006,281: 3614– 3624.
[4] Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 1972,26(4): 239-57.
[5] Schmeiser K , Grand RJ. The fate of E- and P-cadherin during the early stages of apoptosis. Cell Death Differ, 1999,6(4): 377-86.
[6] Steinhusen U, Weiske J, Badock V, et al. Cleavage and Shedding of E-cadherin after Induction of Apoptosis. J. Biol. Chem, 2001, 276: 4972 - 4980.
[7] Brancolini C, Sgorbissa A , Schneider C. Proteolytic processing of the adherens junctions components beta-catenin and gamma-catenin/plakoglobin during apoptosis. Cell Death Differ, 1998, 5(12): 1042-50.
[8] Weiske J, Sch?neberg T, Schr?der W. et al.The Fate of Desmosomal Proteins in Apoptotic Cells. J. Biol. Chem, 2001, 276: 41175 - 41181.
[9] Vicanova J, Mommaas AM, Molder AA. et al. Impaired desquamation in the in vitro reconstructed human epidermis. Cell Tissue Res, 1996,286(1): 115-22.
[10] Haftek M , Simon M , Kanitakis J. et al. Expression of corneodesmosin in the granular layer and stratum corneum of normal and diseased epidermis. Br J Dermatol, Dec 1997,137(6): 864-73.
[1]张正中,张学军,杨森,等.银屑病与细胞凋亡.国际皮肤性病学杂志,2006,(03).
[2]高奎斌,李萍,王雅坤,等.寻常性银屑病患者皮损中Caspase-3和bcl-xL的表达.中华皮肤科杂志,2004,(10).
[3] Keratinocyte apoptosis in epidermal development and disease. D Raj, DE Brash, and D Grossman J Invest Dermatol, Feb 2006; 126(2): 243-57.
[4] Aberrant expression of apoptosis-related molecules in psoriatic epidermis. H Takahashi, A Manabe, A Ishida-Yamamoto, Y Hashimoto, and H IizukaJ Dermatol Sci, Apr 2002; 28(3): 187-97.
[5] Effect of vitamin D3 on the increased expression of Bcl-xL in psoriasis. Y Fukuya, M Higaki, Y Higaki, and M Kawashima Arch Dermatol Res, Feb 2002; 293(12): 620-5.
[6] Alteration of the expression of Bcl-2, Bcl-x, Bax, Fas, and Fas ligand in the involved skin of psoriasis vulgaris following topical anthralin therapy. T Yamamoto and K Nishioka Skin Pharmacol Appl Skin Physiol, Jan 2003; 16(1): 50-8.
[7] Examination of Bcl-2, Bcl-X and bax protein expression in psoriasis. M Kocak, O Bozdogan, E Erkek, P Atasoy, and A Birol Int J Dermatol, October 1, 2003; 42(10): 789-93.
[8] Expression of Bcl-2 family proteins in psoriasis. T Batinac, G Zamolo, I Hadzisejdic, G Zauhar, G Brumini, A Ruzic, and V Persic Croat Med J, Jun 2007; 48(3): 319-26.
[9] Examination of bcl-2 and p53 expressions and apoptotic index by TUNEL method in psoriasis. K Gunduz, P Demireli, S Vatansever, and I Inanir J Cutan Pathol, December 1, 2006; 33(12): 788-92.
[10] Nature of cell kinetics in psoriatic epidermis. FK Doger, E Dikicioglu, F Ergin, E Unal, N Sendur, and M Uslu J Cutan Pathol, March 1, 2007; 34(3): 257-63.
[11] The effects of calcipotriol and methylprednisolone aseponate on bcl-2, p53 and ki-67 expression in psoriasis. E Adisen, A Gulekon, O Erdem, A Dursun, and MA Gurer J Eur Acad Dermatol Venereol, May 1, 2006; 20(5): 527-33.
[12] Expression of antiapoptotic protein c-FLIP is upregulated in psoriasis epidermis. J Yang, Y Li, YQ Liu, JW Long, F Tian, J Dong, GX Shen, YT Tu, and J TaoEur J Dermatol, January 1, 2009; 19(1): 29-33.
[13] Survivin Identifies Keratinocyte Stem Cells and Is Downregulated by Anti-?1 Integrin During Anoikis,Alessandra Marconi, Katiuscia Dallaglio, Roberta Lotti, Cristina Vaschieri, Francesca Truzzi, Fabrizio Fantini, Carlo Pincelli Stem Cells Vol. 25 No. 1 January 2007, pp. 149 -155
[14] Chiodino, C. et al.1999. Communication: expression of the novel inhibitor of apoptosis survivin in normal and neoplastic skin. J. Invest. Dermatol. 113:415-418.
[15] Proliferation, apoptosis, and survivin expression in keratinocytic neoplasms and hyperplasias. AR Bowen, AN Hanks, KJ Murphy, SR Florell, and D Grossman Am J Dermatopathol, June 1, 2004; 26(3): 177-81.
[16] Downregulation of the inhibitor of apoptosis protein survivin in keratinocytes and endothelial cells in psoriasis skin following infliximab therapy. T Markham, C Mathews, S Rogers, R Mullan, B Bresnihan, O Fitzgerald, DJ Veale, and U Fearon Br J Dermatol, Dec 2006; 155(6): 1191-6.
[17] Evaluation of survivin and NF-kappaB in psoriasis, an immunohistochemical study. Asmaa Gaber Abdou and Hayam Mohamed Hanout J Cutan Pathol, November 12, 2007; .
[18] p53 has a direct apoptogenic role at the mitochondria. M Mihara, S Erster, A Zaika, O Petrenko, T Chittenden, P Pancoska, and UM Moll Mol Cell, Mar 2003; 11(3): 577-90.
[19] Expression of p53 protein in psoriasis. W Baran, JC Szepietowski, and G Szybejko-Machaj Acta Dermatovenerol Alp Panonica Adriat, September 1, 2005; 14(3): 79-83.
[20] Expression of p53 in lesions and unaffected skin of patients with plaque-type and guttate psoriasis: a quantitative comparative study. AC Yazici, AA Karabulut, O Ozen, M Eksioglu, and H Ustun
[21] Programmed cell death of keratinocytes in infliximab-treated plaque-type psoriasis. S Kruger-Krasagakis, VK Galanopoulos, L Giannikaki, M Stefanidou, and AD Tosca Br J Dermatol, Mar 2006; 154(3): 460-6.
[22] Apoptosis, P53 and Bcl-2 expression in response to topical calcipotriol therapy for psoriasis. M El-Domyati, M Barakat, R Abdel-Razek, and T El-Din Anbar Int J Dermatol, May 2007; 46(5): 468-74.
[23] Ito Y, Shibata MA, Kusakabe K, Otsuki Y. Method of specific detection of apoptosis using formamide-induced DNA denaturation assay.J Histochem Cytochem. 2006 Jun;54(6):683-92.
[24] Wrone2Smith T, Mita RS, Thomp son CB, et al. Keratinocytes derivedfrom p soriatic p laques are resistant to apop tosis compared with normalskin[ J ]. Am J Pathol, 1997, 151 (5) : 1321 - 1329.
[25] Evaluation of cell death and proliferation in psoriatic epidermis. K Kawashima, H Doi, Y Ito, MA Shibata, R Yoshinaka, and Y Otsuki J Dermatol Sci, Sep 2004; 35(3): 207-14.
[26] [Apoptosis of psoriatic keratinocytes and the severity of patients' condition] J Chen, JY Lu, ZH Tang, CX Zuo, and JH Huang Zhong Nan Da Xue Xue Bao Yi Xue Ban, Dec 2006; 31(6): 936-9.
[2]高奎斌,李萍,王雅坤,等.寻常性银屑病患者皮损中Caspase-3和bcl-xL的表达.中华皮肤科杂志,2004,(10).
[3] Dusek RL , Getsios S, Chen F. The Differentiation-dependent Desmosomal Cadherin Desmoglein 1 Is a Novel Caspase-3 Target That Regulates Apoptosis in Keratinocytes. J. Biol. Chem, 2006,281: 3614– 3624.
[4] Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 1972,26(4): 239-57.
[5] Schmeiser K , Grand RJ. The fate of E- and P-cadherin during the early stages of apoptosis. Cell Death Differ, 1999,6(4): 377-86.
[6] Steinhusen U, Weiske J, Badock V, et al. Cleavage and Shedding of E-cadherin after Induction of Apoptosis. J. Biol. Chem, 2001, 276: 4972 - 4980.
[7] Brancolini C, Sgorbissa A , Schneider C. Proteolytic processing of the adherens junctions components beta-catenin and gamma-catenin/plakoglobin during apoptosis. Cell Death Differ, 1998, 5(12): 1042-50.
[8] Weiske J, Sch?neberg T, Schr?der W. et al.The Fate of Desmosomal Proteins in Apoptotic Cells. J. Biol. Chem, 2001, 276: 41175 - 41181.
[9] Vicanova J, Mommaas AM, Molder AA. et al. Impaired desquamation in the in vitro reconstructed human epidermis. Cell Tissue Res, 1996,286(1): 115-22.
[10] Haftek M , Simon M , Kanitakis J. et al. Expression of corneodesmosin in the granular layer and stratum corneum of normal and diseased epidermis. Br J Dermatol, Dec 1997,137(6): 864-73.
[1]张正中,张学军,杨森,等.银屑病与细胞凋亡.国际皮肤性病学杂志,2006,(03).
[2]高奎斌,李萍,王雅坤,等.寻常性银屑病患者皮损中Caspase-3和bcl-xL的表达.中华皮肤科杂志,2004,(10).
[3] Keratinocyte apoptosis in epidermal development and disease. D Raj, DE Brash, and D Grossman J Invest Dermatol, Feb 2006; 126(2): 243-57.
[4] Aberrant expression of apoptosis-related molecules in psoriatic epidermis. H Takahashi, A Manabe, A Ishida-Yamamoto, Y Hashimoto, and H IizukaJ Dermatol Sci, Apr 2002; 28(3): 187-97.
[5] Effect of vitamin D3 on the increased expression of Bcl-xL in psoriasis. Y Fukuya, M Higaki, Y Higaki, and M Kawashima Arch Dermatol Res, Feb 2002; 293(12): 620-5.
[6] Alteration of the expression of Bcl-2, Bcl-x, Bax, Fas, and Fas ligand in the involved skin of psoriasis vulgaris following topical anthralin therapy. T Yamamoto and K Nishioka Skin Pharmacol Appl Skin Physiol, Jan 2003; 16(1): 50-8.
[7] Examination of Bcl-2, Bcl-X and bax protein expression in psoriasis. M Kocak, O Bozdogan, E Erkek, P Atasoy, and A Birol Int J Dermatol, October 1, 2003; 42(10): 789-93.
[8] Expression of Bcl-2 family proteins in psoriasis. T Batinac, G Zamolo, I Hadzisejdic, G Zauhar, G Brumini, A Ruzic, and V Persic Croat Med J, Jun 2007; 48(3): 319-26.
[9] Examination of bcl-2 and p53 expressions and apoptotic index by TUNEL method in psoriasis. K Gunduz, P Demireli, S Vatansever, and I Inanir J Cutan Pathol, December 1, 2006; 33(12): 788-92.
[10] Nature of cell kinetics in psoriatic epidermis. FK Doger, E Dikicioglu, F Ergin, E Unal, N Sendur, and M Uslu J Cutan Pathol, March 1, 2007; 34(3): 257-63.
[11] The effects of calcipotriol and methylprednisolone aseponate on bcl-2, p53 and ki-67 expression in psoriasis. E Adisen, A Gulekon, O Erdem, A Dursun, and MA Gurer J Eur Acad Dermatol Venereol, May 1, 2006; 20(5): 527-33.
[12] Expression of antiapoptotic protein c-FLIP is upregulated in psoriasis epidermis. J Yang, Y Li, YQ Liu, JW Long, F Tian, J Dong, GX Shen, YT Tu, and J TaoEur J Dermatol, January 1, 2009; 19(1): 29-33.
[13] Survivin Identifies Keratinocyte Stem Cells and Is Downregulated by Anti-?1 Integrin During Anoikis,Alessandra Marconi, Katiuscia Dallaglio, Roberta Lotti, Cristina Vaschieri, Francesca Truzzi, Fabrizio Fantini, Carlo Pincelli Stem Cells Vol. 25 No. 1 January 2007, pp. 149 -155
[14] Chiodino, C. et al.1999. Communication: expression of the novel inhibitor of apoptosis survivin in normal and neoplastic skin. J. Invest. Dermatol. 113:415-418.
[15] Proliferation, apoptosis, and survivin expression in keratinocytic neoplasms and hyperplasias. AR Bowen, AN Hanks, KJ Murphy, SR Florell, and D Grossman Am J Dermatopathol, June 1, 2004; 26(3): 177-81.
[16] Downregulation of the inhibitor of apoptosis protein survivin in keratinocytes and endothelial cells in psoriasis skin following infliximab therapy. T Markham, C Mathews, S Rogers, R Mullan, B Bresnihan, O Fitzgerald, DJ Veale, and U Fearon Br J Dermatol, Dec 2006; 155(6): 1191-6.
[17] Evaluation of survivin and NF-kappaB in psoriasis, an immunohistochemical study. Asmaa Gaber Abdou and Hayam Mohamed Hanout J Cutan Pathol, November 12, 2007; .
[18] p53 has a direct apoptogenic role at the mitochondria. M Mihara, S Erster, A Zaika, O Petrenko, T Chittenden, P Pancoska, and UM Moll Mol Cell, Mar 2003; 11(3): 577-90.
[19] Expression of p53 protein in psoriasis. W Baran, JC Szepietowski, and G Szybejko-Machaj Acta Dermatovenerol Alp Panonica Adriat, September 1, 2005; 14(3): 79-83.
[20] Expression of p53 in lesions and unaffected skin of patients with plaque-type and guttate psoriasis: a quantitative comparative study. AC Yazici, AA Karabulut, O Ozen, M Eksioglu, and H Ustun
[21] Programmed cell death of keratinocytes in infliximab-treated plaque-type psoriasis. S Kruger-Krasagakis, VK Galanopoulos, L Giannikaki, M Stefanidou, and AD Tosca Br J Dermatol, Mar 2006; 154(3): 460-6.
[22] Apoptosis, P53 and Bcl-2 expression in response to topical calcipotriol therapy for psoriasis. M El-Domyati, M Barakat, R Abdel-Razek, and T El-Din Anbar Int J Dermatol, May 2007; 46(5): 468-74.
[23] Ito Y, Shibata MA, Kusakabe K, Otsuki Y. Method of specific detection of apoptosis using formamide-induced DNA denaturation assay.J Histochem Cytochem. 2006 Jun;54(6):683-92.
[24] Wrone2Smith T, Mita RS, Thomp son CB, et al. Keratinocytes derivedfrom p soriatic p laques are resistant to apop tosis compared with normalskin[ J ]. Am J Pathol, 1997, 151 (5) : 1321 - 1329.
[25] Evaluation of cell death and proliferation in psoriatic epidermis. K Kawashima, H Doi, Y Ito, MA Shibata, R Yoshinaka, and Y Otsuki J Dermatol Sci, Sep 2004; 35(3): 207-14.
[26] [Apoptosis of psoriatic keratinocytes and the severity of patients' condition] J Chen, JY Lu, ZH Tang, CX Zuo, and JH Huang Zhong Nan Da Xue Xue Bao Yi Xue Ban, Dec 2006; 31(6): 936-9.