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首页> 外文期刊>Journal of Cellular Physiology >Novel role for the testis‐enriched HSPA2 protein in regulating epidermal keratinocyte differentiation
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Novel role for the testis‐enriched HSPA2 protein in regulating epidermal keratinocyte differentiation

机译：睾丸的小说角色丰富HSPA2应承担的蛋白质在调节表皮角化细胞分化

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摘要

HSPA2, a poorly characterized member of the HSPA (HSP70) chaperone family, is a testis‐enriched protein involved in male germ cell differentiation. Previously, we revealed that HSPA2 is present in human stratified epithelia, including epidermis, however the contribution of this protein to epithelial biology remained unknown. Here, we show for the first time that HSPA2 is expressed in basal epidermal keratinocytes, albeit not in keratinocytes exhibiting features attributed to primitive undifferentiated progenitors, and participates in the keratinocyte differentiation process. We found that HSPA2 is dispensable for protection of HaCaT keratinocytes against heat shock‐induced cytotoxicity. We also shown that lentiviral‐mediated shRNA silencing of HSPA2 expression in HaCaT cells caused a set of phenotypic changes characteristic for keratinocytes committed to terminal differentiation such as reduced clonogenic potential, impaired adhesiveness and increased basal and confluency‐induced expression of differentiation markers. Moreover, the fraction of undifferentiated cells that rapidly adhered to collagen IV was less numerous in HSPA2‐deficient cells than in the control. In a 3D reconstructed human epidermis model, HSPA2 deficiency resulted in accelerated development of a filaggrin‐positive layer. Collectively, our results clearly show a link between HSPA2 expression and maintenance of keratinocytes in an undifferentiated state in the basal layer of the epidermis. It seems that HSPA2 could retain keratinocytes from premature entry into the terminal differentiation process. Overall, HSPA2 appears to be necessary for controlling development of properly stratified epidermis and thus for maintenance of skin homeostasis.
机译：HSPA2,糟糕的HSPA特点(HSP70)伴侣的家庭,是一个睾丸蛋白质参与男性生殖细胞分化。HSPA2存在于人类的复层上皮细胞,然而包括表皮的贡献这种蛋白质上皮生物学未知的。HSPA2基底表皮中表达角化细胞,尽管不是在角化细胞表现出的特性归因于原始未分化的祖细胞,并参与角化细胞分化过程。发现HSPA2可有可无的保护HaCaT角质细胞对热休克诱导细胞毒性。慢病毒介导的HSPA2 shRNA沉默HaCaT细胞表达一组引起的表型变化的特征角化细胞致力于终端分化,如减少了单独使用潜力,受损的粘性,增加基底和confluency诱导表达分化标记。未分化的细胞,迅速地坚持胶原IV是HSPA2少很多的不足细胞比控制。人类表皮模型,HSPA2不足导致在加速发展并积极的层。结果清楚地表明HSPA2之间的联系角化细胞的表达和维护未分化状态的基底层表皮。角化细胞过早进入终端分化的过程。似乎是必要的控制正确分层表皮和发展因此,对于维护皮肤内稳态。

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