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

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...

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Bibliographic Details
Published in:Journal of cellular physiology 2018-03, Vol.233 (3), p.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: Article
Language:English
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
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Summary: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.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.26142