The hsp27 kD heat shock protein and p38-MAPK signaling are required for regular epidermal differentiation
The hsp27 kD heat shock protein and p38-MAPK signaling are required for regular epidermal differentiation
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DOI：
10.1016/j.jdermsci.2010.10.009
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发表时间：
2011-01-01
影响因子：
4.6
通讯作者：
Trautinger, Franz
中科院分区：
文献类型：
--
作者：
Jonak, Constanze;Mildner, Michael;Trautinger, Franz
背景资料：hsp 27在人表皮角质形成细胞中的表达与体外和原位分化密切相关。目的：通过siRNA特异性抑制hsp 27的表达和p38-MAPK抑制hsp 27的表达，进一步了解hsp 27在表皮分化中的作用。方法：采用正常人角质形成细胞（KC）和器官型皮肤培养物（SE皮肤等效物）。在这些模型中，hsp 27的表达和磷酸化分别被siRNA和p38-MAPK的特异性抑制剂SB 203580抑制。结果：抑制p38-MAPK可下调KC和SE中hsp 27的表达。此外，在SB 203580的存在下，Ca 2+诱导的前聚丝蛋白和兜甲蛋白的表达在蛋白水平上被抑制，并且聚丝蛋白、角蛋白10和转氨酶1的表达在mRNA水平上被抑制。在SE中加入SB 203580和hsp 27基因敲除均导致角质形成细胞分化不规则、表皮层结构紊乱和K10表达延迟。结论：hsp 27的表达及其p38-MAPK的磷酸化是角质形成细胞分化和表皮层结构形成所必需的。(c)2010年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: In human epidermal keratinocytes the expression of hsp27 is closely related to differentiation in vitro and in situ.Objective: We aimed to gain further insight into the role of hsp27 in epidermal differentiation by specific inhibition through siRNA and inhibition of p38-MAPK. the key enzyme of hsp27 phosphorylation.Methods: Normal human keratinocytes (KC) and organotypic skin cultures (SE-skin equivalents) were used. Expression and phosphorylation of hsp27 was inhibited in these models by siRNA and SB203580, a specific inhibitor of p38-MAPK, respectively. Modification of morphology and expression of hsp27 and other differentiation associated proteins was investigated by immunofluorescence, western blot, and RT-PCR.Results: Inhibition of p38-MAPK resulted in a downregulation of hsp27 in KC and SE. Additionally, in the presence of SB203580 Ca2+ induced expression of pro-filaggrin and loricrin was inhibited at the protein level and expression of filaggrin, keratin 10, and transglutaminase 1 at the mRNA level. Addition of SB203580 to SE, as well as hsp27 knockdown in this model resulted in identical patterns of irregular differentiation, disturbance of epidermal layers, and delayed expression of K10.Conclusion: These results provide evidence that the expression of hsp27 and its phosphorylation by p38-MAPK are required for keratinocyte differentiation and for the formation of a regularly stratified epidermis. (c) 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.