Annexin A2介导毛乳头细胞凝集生长在毛发再生中的作用及机制研究

The development of hair follicle and its cell cycle regulation depend on the interaction of dermal papilla cells(DPCs) and hair matrix cell. Dermal papillae cells play a important role by the autocrine and paracrinein of many growth factors. We firstly found that annexin a2 was upregulated in dermal papillae cells with aggregation by proteomics technology. RNA interference, gene recombination technology and cytology had confirmed that annexin A2 could promote the proliferation of dermal papillae cells and play important roles in the aggregation.of dermal papillae cells. This project is to capture the proteins interacted with annexin a2 in dermal papillae cells by co-Immunoprecipitation assay, to study the roles of interest proteins in regulating and controlling annexin A2. The study would contribute to clarify the concrete molecular mechanism in regulating the biological function of aggregation of dermal papillae cells and clear the roles of Annexin A2 in hair regeneration. The study provide the foundation for further study of the roles of annexin A2 in follicle development and hair follicle cycle regulation and provide the new ideas for the treatment of hair diseases.

毛囊发育和毛发再生依赖毛囊上皮和毛乳头的相互作用，毛乳头通过自分泌或旁分泌多种信号分子在其中发挥关键作用。申请者采用蛋白组学技术首次发现Annexin A2在凝集生长的毛乳头细胞特异性高表达，经RNAi、基因重组及细胞学研究表明，Annexin A2显著促进细胞增殖，与毛乳头细胞的凝集生长密切相关。本课题拟通过pull-down试验和免疫共沉淀技术，抗Annexin A2抗体为诱饵蛋白，捕获毛乳头细胞中与Annexin A2相互作用蛋白，研究目的蛋白对Annexin A2的调控作用。本项目可阐明Annexin A2介导毛乳头细胞凝集生长的分子机制，明确Annexin A2在毛发再生中的作用，为深入研究Annexin A2在毛囊发育及周期调控中的作用奠定基础，也可为毛发疾病的治疗提供新思路。

毛囊是可再生器官，毛囊的每一个生长周期都是器官再生的完整过程，毛囊发育和毛发再生依赖毛囊上皮和毛乳头的相互作用。毛乳头具有干细胞特性，在毛囊的生长发育和周期调控中发挥关键作用。在前期工作中本课题组采用蛋白组学技术首次发现Annexin A2在凝集生长的毛乳头细胞特异性高表达。本项目的主要研究内容：1、Annexin A2的表达抑制/过表达对毛乳头细胞生长的影响：经RNAi、基因重组及细胞学研究表明，Annexin A2显著促进毛乳头细胞增殖，与毛乳头细胞的凝集生长密切相关。2、与Annexin A2相互作用蛋白质研究：通过免疫共沉淀技术，抗Annexin A2抗体为诱饵蛋白，捕获毛乳头细胞中与Annexin A2相互作用蛋白，发现与Annexin A2相互作用的蛋白质，包括Wnt1、Wnt5a和ß-catenin。3、Annexin A2在毛乳头细胞凝集生长中的作用机制研究：通过分析Annexin A2与Wnt1、Wnt5a和ß-catenin的相互作用，我们得出Annexin A2通过Wnt/ß-catenin 信号通路发挥作用，而Wnt/ß-catenin信号通路是毛囊周期循环重要的调节通路，Annexin A2可能在毛乳头和毛囊周期循环中发挥重要作用，对脱发疾病的治疗提供可能的靶点。