Novel role for the testis-enriched HSPA2 protein in regulating epidermal keratinocyte differentiation.

a poorly characterized member of the (HSP70) chaperone family, is a testis-enriched protein involved in male germ cell differentiation. Previously, we revealed that 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 Hduanyu18422 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 Hduanyu18422 is dispensable for protection of HaCaT keratinocytes against heat shock-induced cytotoxicity. We also shown that lentiviral-mediated shRNA silencing of Hduanyu18422 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 cells than in the control. In a 3D reconstructed human epidermis model, Hduanyu18422 deficiency resulted in accelerated development of a filaggrin-positive layer. Collectively, our results clearly show a link between Hduanyu18422 expression and maintenance of keratinocytes in an undifferentiated state in the basal layer of the epidermis. It seems that Hduanyu18422 could retain keratinocytes from premature entry into the terminal differentiation process. Overall, Hduanyu18422 appears to be necessary for controlling development of properly stratified epidermis and thus for maintenance of skin homeostasis.

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