Fu Haijing, Wu Chenxi, Xu Tianyi, Zhao Wumei, Jiang Leiwei, Shan Shijun
Department of Dermatology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361000, China.
Department of Dermatology, Guizhou Provincial People's Hospital, Guiyang 550002, China; GuiYang First People Hospital, Guiyang 550002, China.
Biochim Biophys Acta Mol Cell Res. 2025 Dec;1872(8):120033. doi: 10.1016/j.bbamcr.2025.120033. Epub 2025 Jul 31.
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.
雄激素性脱发（AGA）是最常见的一种型态性脱发，其通过雄激素敏感性、年龄依赖性进展和遗传易感性表现出来。新出现的证据表明，微小RNA在毛囊病理生理学中是关键的转录后调节因子。本研究使用人毛囊干细胞（HFSCs）、AGA患者的毛囊样本和AGA小鼠模型来探究miR-22-3p/CLIC4信号通路在AGA中的作用。在5级AGA患者的秃发毛囊中观察到miR-22-3p表达显著升高。然后我们确定氯离子细胞内通道4（CLIC4）是miR-22-3p的一个新靶点，且CLIC4在AGA患者的秃发毛囊中明显低表达。功能研究表明，敲低CLIC4（shCLIC4）会损害HFSCs的增殖能力并破坏音猬因子（SHH）信号通路的激活，这可通过Gli1和Gli2转录活性降低得到证明。这些发现确立了miR-22-3p/CLIC4轴是毛囊小型化的一种新型调节因子，提出CLIC4介导的SHH调节作为AGA干预的潜在治疗靶点。
