Collagen type V alpha 3 chain is involved in human skin basement membrane physiology and MMP‐9 regulation

Abstract Objective Collagens are widely studied proteins given their implications in the skin extracellular matrix and pathological conditions such as fibrosis. Type V collagen is a member of the fibrillar collagens, and three different polypeptide chains, α1, α2 and α3 form isoforms through associations. The third chain, α3, of type V collagen was initially identified in the placenta, but after decades, it remains poorly characterized. The aim of this study is to investigate the expression and localization of the α3 chain of type V collagen in the skin and its evolution during skin aging. The identification of α3(V) collagen as a target of retinoic acid and its interaction with matrix metalloproteinase‐9 (MMP‐9) was investigated. Methods The expression and localization of α3(V) collagen were assessed by immunodetection in ex vivo skin and in keratinocytes using a calcium‐differentiated model. The variation in α3(V) collagen expression during aging was studied in ex vivo skin from donors of different ages. The modulation of α3(V) collagen by retinoic acid was investigated by qPCR in keratinocytes and by immunofluorescence in ex vivo skin biopsies. Silencing of α3(V) collagen was performed using siRNA. The expression of MMP‐9 was investigated using qPCR. Results In our study, we showed that α3(V) collagen was abundantly produced by basal skin keratinocytes and in the outer root sheath of the hair. α3(V) collagen expression appears to decrease with age in the skin and in differentiated keratinocytes. We also identified that treatment of keratinocytes and ex vivo skin biopsies with retinoic acid induced α3(V) collagen expression. Finally, we showed that inhibition of α3(V) collagen in keratinocytes led to an increase in MMP‐9 expression. Conclusion This study provides a better understanding of α3(V) collagen expression and localization in the skin. These findings suggest that α3(V) collagen could contribute to the therapeutic and anti‐aging value of retinoic acid on the skin and may open new prospects. Finally, our data shed more light on the functional relationship between α3(V) collagen and MMP‐9, opening possibilities for anti‐aging and eczema treatments.