Fgf21 Deficiency Delays Hair Follicle Cycling and Modulates miRNA–Target Gene Interactions in Mice

Fibroblast growth factor 21 (<i>Fgf21</i>) is a key regulator of hair follicle development and cycling. Although microRNAs (miRNAs) are involved in this process, the specific mechanisms through which <i>Fgf21</i> regulates hair follicle growth remain unclear. This study investigates the role of <i>Fgf21</i> and its associated miRNAs in hair follicle growth and development. Using CRISPR/Cas9, we generated <i>Fgf21</i> knockout mice (<i>Fgf21^-/^-</i>), which exhibited a delayed transition from the telogen to anagen phases compared to wild-type (WT) mice. miRNA sequencing identified differentially expressed miRNAs in <i>Fgf21</i>^-/^- mice, with dual-luciferase assays confirming that miR-134-5p directly targets vascular endothelial zinc finger 1 (Vezf1) and miR-136-5p targets mitogen-activated protein kinase kinase kinase 1 (Map3k1). Real-time qPCR analysis revealed that Vezf1 and Map3k1 expression was higher in <i>Fgf21^-/^-</i> mice than in WT mice during catagen, but lower during telogen. These findings indicate that <i>Fgf21</i> plays a critical role in regulating hair follicle growth and may modulate Vezf1 and Map3k1 expression through miRNAs. This study provides novel insights into the molecular regulation of hair follicle growth and suggests potential therapeutic strategies for hair follicle-related disorders.