In skin, epidermal basement membrane zone (BMZ) serves as a niche for epidermal stem cells and is vital to cell homeostasis regulation. Type XVII collagen (COL17) is a hemidesmosomal protein located at the epidermal BMZ. COL17 deficiency in mice and human exhibits early aged phenotype as gray hair and hair loss. In this context, COL17 has been known to engage in maintaining melanocyte stem cells and hair follicle stem cells. However, the role of COL17 in regulating stem cells in interfollicular epidermis has not been elucidated. Here we show that COL17 controls epidermal proliferation through Wnt signaling. Loss of COL17 in interfollicular epidermis leads to epidermal hyperproliferation due to aberrant Wnt signaling. Furthermore, COL17 distribution in epidermal basal cells alters with aging, and this change also induces epidermal hyperproliferation. Of particular interest is the fact that overexpression of human COL17 in aged mice epidermis restores COL17 distribution and amends epidermal hyperproliferation. These findings demonstrate that COL17 is crucial for maintaining epidermal homeostasis. Our study implicates that faulty epidermal BMZ is involved in uncontrolled cell proliferation, phenocopying aged skin and oncogenesis.

Type XVII collagen suppresses interfollicular epidermal proliferation in neonatal and aged skin, and helps rejuvenate epidermis