毛囊干细胞AR基因调控毛发形成和生长在AGA脱发中的作用及机制研究

雄激素源性脱发（AGA）是影响患者身心健康的常见难治性疾病。自体毛发移植是一有效治疗手段，但为何非脱发区毛发移植到脱发区其不再脱落？AR表达差异是一重要因素，目前机制不明。毛囊干细胞（HFSC）在毛囊生长周期中起重要作用,我们前期研究发现，脱发区β-catenin表达和HFSC增殖活性降低及其AR表达增加。已证明Wnt/β-catenin信号通路与HFSC增殖和毛囊周期性变化密切相关。在此基础上，本课题拟用基因转染和沉默技术建立AR过表达和沉默的HFSC，在雄激素刺激后测定Wnt/β-catenin信号通路蛋白表达；通过在体生物成像技术示踪植入裸鼠皮肤的AR沉默或过表达的HSFC，实时监测其在不同干扰因素作用下，在体分化为毛囊的能力和对毛发生长的影响及其与Wnt/β-catenin通路变化关系。以此探讨HFSC AR 过表达与AGA发病关系及其机制，为开发新的AGA治疗靶点的药物提供思路。

Androgenetic Alopecia（AGA）is a common intractable disease with negative psychological impact on affected individuals, due to a remarkable reduction of life quality. Autologous hair transplantation is one of effective treatments, and it's meaningful that the hair-units transplanted from healthy area no longer fall in alopecia district. Differential expression of androgen receptor（AR） is an important factor，but the mechanism is still unclear. Hair follicle stem cells ( HFSC ) play an important role in the growth cycle of hair follicles. Our previous studies have unveiled that mRNA expression level of β-catenin decreased, HFSC proliferative activity reduced and AR expression increased in hair loss area of androgenetic alopecia patients. It is proved that Wnt /β- catenin signal pathway is closely related to HFSC proliferation and hair follicle cyclical changes. On this basis, our project intends to establish AR over-expression and silencing HFCS by gene transfection and silencing, respectively measuring the expression of Wnt /β-catenin signaling pathway protein after the stimulation of dihydrotestosterone (DHT); real-time monitoring the variation of its ability that in vivo differentiating of hair follicles and influence on hair growth with the Wnt /β-catenin pathway under different disturbance factors, by the mean of vivo biological imaging technology which trace the AR over-expression or silencing HSFC in nude mice skin. We are aiming at casting light on the molecular mechanism of AGA and its association with the HFCS AR over-expression. And the progress in this area of research will hopefully lead to the development of new therapeutic approaches in the treatment of hair growth disorders.