Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair

Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair
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DOI:
10.1111/j.1365-2133.2012.10885.x
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发表时间:
2012-06-01
影响因子:
10.3
通讯作者:
Zeeuwen, P. L. J. M.
Zeeuwen, P. L. J. M.
中科院分区:
医学1区
文献类型:
--
作者:
de Koning, H. D.;van den Bogaard, E. H.;Zeeuwen, P. L. J. M.

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研究背景近年来的研究强调了遗传性和获得性皮肤屏障异常在银屑病和特应性皮炎等常见炎症性疾病中的重要性。迄今为止,还没有关于实验性屏障破坏对角质形成细胞膜蛋白表达的影响的全面研究。目的分析实验性皮肤屏障破坏对角质形成细胞膜结构蛋白和角质形成细胞分化调节蛋白表达的影响。(第1、3和7天)和蛋白质(第1、2、4和9天)在正常皮肤上施用十二烷基硫酸钠(SDS)后结构蛋白和调节分子的表达水平,用胶带剥离银屑病和AD患者及健康对照的未受累表皮。结果胶带剥离后,一些结构分子被显著下调,(在mRNA水平以及蛋白质水平上),包括LCE 5A、LCE 2B、FLG、FLG 2和LOR,而其他的被上调:IVL、SPRR1、SPRR2、HRNR和最显著的LCE3A。表皮交联酶TGM1、TGM3和TGM5均上调,而参与脱屑过程的蛋白酶(CTSV、KLK 5和KLK 7)下调或不受影响。SDS诱发的刺激性接触性皮炎的大多数结果相似。银屑病和AD患者的正常表皮和非皮损皮肤之间的反应没有显着差异。结论皮肤屏障破坏诱导的临时屏障修复反应,包括增加的几个cornification-related蛋白的表达,和一些结构和脱屑相关蛋白的表达下降。
Background Recent studies have emphasized the importance of heritable and acquired skin barrier abnormalities in common inflammatory diseases such as psoriasis and atopic dermatitis (AD). To date, no comprehensive studies on the effect of experimental barrier disruption on cornified envelope protein expression have been performed.Objectives To analyse the effect of experimental skin barrier disruption on the expression of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins.Methods We examined mRNA (day 1, 3 and 7) and protein (day 1, 2, 4 and 9) expression levels of structural proteins and regulatory molecules after sodium dodecyl sulphate (SDS) application on normal skin, and tape stripping of uninvolved epidermis of patients with psoriasis and AD and healthy controls.Results Upon tape stripping, several structural molecules were significantly down-regulated (at the mRNA level as well as the protein level), including LCE5A, LCE2B, FLG, FLG2 and LOR, whereas others were upregulated: IVL, SPRR1, SPRR2, HRNR and most notably LCE3A. The epidermal crosslinking enzymes TGM1, TGM3 and TGM5 were all upregulated, whereas proteases involved in the desquamation process (CTSV, KLK5 and KLK7) were downregulated or unaffected. Most results were similar in SDS-instigated irritant contact dermatitis. There was no significant difference in response between normal epidermis and nonlesional skin of patients with psoriasis and AD.Conclusions Skin barrier disruption induces a temporary barrier repair response composed of increased expression of several cornification-related proteins, and decreased expression of some structural and desquamation-related proteins.