Bowen Zhang,1,2 Xue He,1,2 Yaxin Guo,1,2 Shengnan Zhao,1,2 Jing Lan,1,2 Fuqiang Chen,1,2 Long Wan,3 Haishan Tian,4 Xuegang Xu1,2 

1Department of Dermatology, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Key Laboratory of Immunodermatology, Ministry of Education and NHC; National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, People’s Republic of China; 3Department of Pharmacy, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 4School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, People’s Republic of China

Correspondence: Xuegang Xu, Department of Dermatology, The First Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People’s Republic of China, Email xuxuegang2749290@163.com

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-β 2, TGF-β 3, 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.

Keywords: fibroblast growth factor 9, hair growth, hair follicle, TGF-β/BMP/Smad pathway