雄激素性脱发的重要原因是⽑囊周期紊乱，研究证实雄激素能诱导毛囊细胞分泌Dickkopf-1(DKK1)增加，阻断Wnt通路而缩短毛囊生长周期，进而引起脱发。全基因组关联分析发现其同源家族成员DKK2基因是雄激素性脱发的易感基因。我们的前期研究已证实DKK2依赖Wnt通路调控毛囊生长并参与毛囊周期转化，但DKK2在雄激素性脱发中的作用和机制不清楚。我们推测：雄激素性脱发中，雄激素二氢睾酮升高引起毛乳头细胞分泌DKK2增加并与毛囊上皮细胞膜的Wnt受体-低密度脂蛋白受体相关蛋白结合，促进受体内吞，阻断Wnt信号通路，抑制上皮细胞增殖并促进其凋亡，进而缩短毛囊周期引起脱发。本项目拟利用雄激素性脱发临床病例验证DKK2通过调节Wnt通路参与雄激素性脱发发生发展过程；建立小鼠雄激素性脱发模型，在体验证DKK2参与雄激素性脱发的作用和机制，以探讨DKK2作为逆转雄激素性脱发的新型药物靶点的可行性。

An important cause of androgenetic alopecia is the disorder of hair growth cycle. Studies have shown that androgen could induce the increase of Dickkopf-1 (DKK1) secretion by hair follicle cells, block the Wnt pathway and shorten the hair follicle growth cycle, thereby causing hair loss. Genome-Wide Association Studies revealed that its homologous family member DKK2 gene is a susceptible gene for androgenetic alopecia. Our previous studies have confirmed that DKK2 relies on the Wnt pathway to regulate hair follicle growth and participate in hair follicle cycle transition, but the role and mechanism of DKK2 in androgenetic alopecia are unclear. We speculate that in androgenetic alopecia, an increase in androgen dihydrotestosterone causes the increase of DKK2 secretion from dermal papilla cells and DKK2 binds to the Wnt receptor-low-density lipoprotein receptor-related protein of the hair follicle epithelial cell membrane, promoting receptor endocytosis and block the Wnt signal pathway, which inhibit epithelial cell proliferation and promote its apoptosis, thereby shortening the hair growth cycle and causing hair loss. This project intends to use androgenic alopecia clinical samples to verify that DKK2 participates in the process of androgenetic alopecia by regulating the Wnt pathway; establish a mouse model of androgenetic alopecia and verify in vivo the role and mechanism of DKK2 in androgenetic alopecia to explore the feasibility of DKK2 as a new drug target to reverse androgen-induced alopecia.