Human Fibroblast Growth Factor 9 Induces Hair Follicle Cycle Transition via TGF-β/BMP/Smad Pathway

Abstract

Background: Fibroblast growth factor 9 (FGF9) is a crucial regulator of hair follicle development; however, the precise regulatory role of FGF9 on the biological behavior of hair follicles remains unclear. Purpose: Explore the effects of recombinant human fibroblast growth factor (rhFGF9) on hair follicle growth and cycle transition in mice, as well as the associated mechanisms. Methods: We utilized soluble recombinant human fibroblast growth factor 9 (rhFGF9), expressed in Escherichia coli, and injected it into the dorsal skin of mice. RNA sequencing (RNA-seq) was employed to identify differentially expressed genes and associated key metabolic pathways in skin tissue. Additionally, immunohistochemistry, quantitative PCR (qPCR), and Western blotting techniques were applied to assess the expression of factors related to metabolic pathways across different groups. Results: RhFGF9 stimulated hair growth by inducing the anagen phase in C57BL/6 N mice. Histological analysis revealed that intradermal injections of rhFGF9 enhanced hair follicle development. Transcriptomic analysis revealed that the mechanism underlying this effect might involve the transforming growth factor-β (TGF-β) signaling pathway. Immunohistochemistry, quantitative PCR, and Western blot analyses further demonstrated the upregulation of TGF-β2, TGF-β3, bone morphogenetic protein 4 (BMP4), and pSmad2 expression in the experimental group. Conclusion: These results indicate that rhFGF9 might promote hair growth via the TGF-β/BMP/Smad signaling pathway and highlight its potential as a therapeutic option for treating hair loss.