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

• Published in: Journal of cellular physiology Vol. 233; no. 3; pp. 2629 - 2644
• Main Authors: Gogler‐Pigłowska, Agnieszka, Klarzyńska, Katarzyna, Sojka, Damian R., Habryka, Anna, Głowala‐Kosińska, Magdalena, Herok, Marcin, Kryj, Mariusz, Halczok, Monika, Krawczyk, Zdzisław, Scieglinska, Dorota
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-03-2018
• Subjects: Adult; Aged; Aged, 80 and over; Cell Adhesion; Cell Differentiation; Cell Line; Cell Proliferation; Collagen (type IV); Collagen Type IV - metabolism; cytoprotection; Cytotoxicity; differentiation; Differentiation (biology); Epidermis; Epidermis - metabolism; Epidermis - pathology; Female; Filaggrin; Gene Expression Regulation; Heat shock; Heat-Shock Response; Homeostasis; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; HSPA2; Humans; Intermediate Filament Proteins - metabolism; Keratinocytes; Keratinocytes - metabolism; Keratinocytes - pathology; Male; Middle Aged; Phenotype; Proteins; RNA Interference; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Skin; Three dimensional models; Toxicity; Transfection; differentiation; HSPA2; keratinocytes; cytoprotection; epidermis
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26142

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.
In human skin HSPA2 is preferentially expressed in basal epidermal keratinocytes. HSPA2 is dispensable for protection of HaCaT keratinocytes against heat shock‐induced cytotoxicity. HSPA2 participates in the keratinocyte differentiation process.