FGF22 Secreted by Hair Papilla Cells Regulates Hair Follicle Stem Cell Proliferation and Differentiation

Hair follicle stem cells (HFSCs) are resident stem cells within hair follicles (HFs) that possess self-renewal and differentiation capacities, serving as a critical model for regenerative medicine research. Their dynamic interaction with dermal papilla cells (DPCs) plays a decisive role in HF development and cycling. <i>FGF22</i> is a paracrine fibroblast growth factor that can regulate the proliferation, differentiation and migration of epithelial cells. This study established a DPC-HFSC co-culture system, revealing that <i>FGF22</i> overexpression in DPCs significantly upregulated <i>FGFR1</i>/<i>FGFR2</i> mRNA expression levels in HFSCs (<i>p</i> < 0.05), with a 1.67-fold increase in EdU-positive cell proportion (<i>p</i> < 0.01). CCK-8 assays demonstrated markedly enhanced HFSC viability (<i>p</i> < 0.01), with a 17% reduction in HFSC apoptosis (<i>p</i> < 0.05). Conversely, <i>FGF22</i> knockout downregulated <i>FGFR1/FGFR2</i> expression (<i>p</i> < 0.05), reduced HFSC proliferation capacity by 25% (<i>p</i> < 0.01), and increased HFSC apoptosis levels by 1.81-fold (<i>p</i> < 0.05). In addition, <i>FGF22</i> overexpression promotes the proliferation and differentiation of HFSCs by activating Wnt/β-Catenin, Sonic Hedgehog (Shh) and Notch signaling pathways, or inhibiting BMP signaling pathways. Knockout of <i>FGF22</i> weakens these processes and inhibits the activation and differentiation of HFSCs. This study, through the DPCs-HFSCs co-culture system, revealed the regulatory mechanism of <i>FGF22</i> secreted by DPCs on the proliferation and differentiation of HFSCs, thereby providing theoretical references for fields such as fine-wool sheep breeding, human regenerative medicine, and hair loss treatment.