FGF5 promotes catagen induction through upregulation of TGF-β2 in human dermal papilla cells.

Fibroblast growth factor 5 (FGF5) has been implicated in catagen induction, but its downstream mechanism remains unclear. Transforming growth factor-β2 (TGF-β2), another catagen-inducing factor, contributes to follicular epithelial cell apoptosis and regression of the lower portion of the hair follicle during catagen. This study examined whether TGF-β2 acts downstream of FGF5 signaling in human dermal papilla cells. FGF5 did not reduce keratinocyte viability, whereas TGF-β2 markedly decreased viability. In dermal papilla cells, FGF5 increased TGF-β2 expression, whereas FGF1 and FGF2 did not. These findings suggest that FGF5 may act upstream of TGF-β2 rather than as a direct final effector of follicular epithelial cell death. FGF5-induced TGF-β2 upregulation was suppressed by FGFR1 inhibition, p38 MAPK and Akt inhibition, and ETS-1 knockdown, but not by MEK/ERK inhibition. FGF5 did not markedly increase STAT3 phosphorylation. Cyclosporine A, which prolongs anagen in human hair follicles, reduced FGF5 expression in dermal papilla cells but not in outer root sheath cells. Together, these findings suggest that FGF5 may contribute to catagen induction indirectly by upregulating TGF-β2 expression in dermal papilla cells through FGFR1-dependent signaling involving p38 MAPK, Akt, and ETS-1.