MicroRNA-22-3p suppresses hair regrowth in androgenetic alopecia by targeting chloride intracellular channel 4.

Androgenetic alopecia (AGA), the most prevalent form of patterned hair loss, manifests through androgen sensitivity, age-dependent progression, and genetic predisposition. Emerging evidence highlights microRNAs as critical post-transcriptional regulators in hair follicle pathophysiology. This study used human hair follicle stem cells (HFSCs), hair follicle samples of AGA patients and AGA mouse model to explore the role of miR-22-3p/CLIC4 signaling in AGA. A significant rise in miR-22-3p expression was observed in balding hair follicles of grade 5 AGA patients. Then we identify chloride intracellular channel 4 (CLIC4) as a novel target of miR-22-3p and CLIC4 is markedly low expressed in balding hair follicle of AGA patients. Functional studies demonstrated that knockdown CLIC4 (shCLIC4) impaired HFSCs proliferative capacity and disrupted sonic hedgehog (SHH) pathway activation, evidenced by decreased Gli1 and Gli2 transcriptional activity. These findings establish the miR-22-3p/CLIC4 axis as a novel regulator of hair follicular miniaturization, proposing CLIC4-mediated SHH modulation as a potential therapeutic target for AGA intervention.