垂体瘤转化基因PTTG1及其结合因子PBF在雄激素源性脱发中的作用及机制研究

Androgenetic alopecia (AGA), or male-pattern hair loss (MPHL), is a genetically determined slowly progressive form of alopecia which begins after the onset of puberty. The prevalence increases with advancing age. AGA carry deep social implications for the affected individual due to the significant changes it can cause in the outward appearance of the patient. Hair loss results in reduced self esteem, loss of confidence and anxiety in affected men. However, there are many side effects of current oral and topical medications. Therefore it is desirable and urgent to furtherly understand the mechanism of AGA and find more safe and effective treatments. Pituitary tumor transforming gene (PTTG1) encodes for securin, a protein involved in several metabolic reactions, cell cycle progression and appropriate cell division. Previous studies have showed that the expression of PTTG1 correlates with cell proliferation and angiogenesis. PTTG1 protein is overexpressed in many tumors and serves as a new proliferation marker. PTTG1 binding factor (PBF) is regarded to bind PTTG1 and promote its nuclear translocation. Anagen angiogenesis is required for hair growth. Therefore we hypothesize that: PTTG1/PBF may mediate the anagen hair angiogenesis, regulate hair growth and participate the pathogenesis of AGA. This project aims to investigate the expression and function of PTTG1 and PBF in AGA by employing AGA scalp ex vivo, primary hair follicle cell cuture in vitro and animal model in vivo. In conclusion, through this study, we may find novel pathway to the pathogenesis of AGA and possible novel targets to future therapy.

雄激素源性脱发（AGA）是成人脱发最常见的类型，目前其发病机制仍不明确。AGA患病率极高，而治疗方法却非常有限，且现有治疗药物存在较大的不良反应和潜在的致癌风险。因此，如何深化对雄激素源性脱发发病机制的认识和理解，从而找到更加安全有效的治疗方法是目前医学研究的一个重要课题。垂体瘤转化基因（PTTG1）高度表达于多种肿瘤组织，研究表明：PTTG1的表达与细胞的增殖状态和血管新生密切相关；PTTG结合因子（PBF）的主要功能是与PTTG1结合，促进PTTG1转位至细胞核内。我们前期研究发现：PTTG1/PBF均表达于毛囊细胞。由于毛周血管新生是毛发生长的必备条件，所以我们推测：PTTG1/PBF很可能参与毛发生长调节，从而介导雄激素源性脱发的发病。本研究拟通过离体患者皮损、体外毛囊细胞培养以及小鼠模型实验，探索PTTG1及PBF蛋白在雄激素源性脱发发病中的机制及意义，以期发现新的治疗靶点。

垂体瘤转化基因（PTTG1）高度表达于多种肿瘤组织，是恶性肿瘤潜在生物学标记之一，同时也是细胞周期调控蛋白。我们研究发现：PTTG1/PBF不仅表达于银屑病、脂溢性角化病（SK）、基底细胞癌（BCC）和鳞状细胞癌（SCC）等组织和细胞，更表达于毛囊细胞；PTTG1是增殖性皮肤病的生物学标记之一，参与细胞周期调控，可能参与毛发生长调节。原代培养正常及银屑病角质细胞中，PTTG1位于胞浆。HaCat细胞分裂中期，PTTG1分布于整个胞浆。G2期和M期都可见表达，PTTG1的表达量与细胞周期蛋白B1（cyclin B1）的表达量及M期核多形性的程度成正相关。PTTG1 siRNA能够降低A431细胞的侵袭能力。因此，我们通过皮肤标本，并进行角质细胞原代培养，以及免疫组化、免疫荧光，定量PCR、小鼠模型实验等方法，探索PTTG1/PBF的亚细胞定位以及其在细胞周期、毛发生长中的作用机制。