MTA2在睾丸支持细胞（Sertoli cells）中的功能和机制研究

项目名称： MTA2在睾丸支持细胞（Sertoli cells）中的功能和机制研究

项目编号： No.31271248

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 李伟

作者单位： 中国人民解放军第四军医大学

项目金额： 80万元

中文摘要： 精子发生过程中，作为生精小管内唯一与生精细胞接触的体细胞，支持细胞（SCs）对生精细胞的发育分化起着重要的干预调节作用。大量文献表明，机体可以通过去乙酰化修饰机制对SCs关键性基因进行重要调控。我们前期研究显示组蛋白去乙酰化酶募集分子MTA2在SCs中特异性表达，这种表达受雄激素调节；MTA2参与了FSH对其受体的转录抑制调节；在以唯支持细胞综合征为代表的严重生精障碍的睾丸病理组织中MTA2的表达锐减，提示后者可能参与其病理发生。本课题拟在此基础上进一步研究MTA2与FSH、雄激素信号通路的作用关系，体外、体内干涉MTA2的表达后观察对各级生精细胞发育、分化的影响，继而深入研究其作用机制，尤其是与组蛋白去乙酰化酶HDACs的作用关系。这些研究可以阐明MTA2在SCs上特异性表达的功能意义，揭示其作用机制，并有助于发现SCs通过MTA信号通路调控生精细胞增殖分化的新机制，具有重要理论意义。

中文关键词： 肿瘤转移相关蛋白2；支持细胞；去乙酰化修饰；转录调控；精子发生

英文摘要： Sertoli cells (SCs),characterized as the only somatic cells possessing close structural relationship with germ cells inside the seminiferous tubules, have drawn much attention of reproductive researchers because of their pivotal roles in the regulation of spermatogenic proliferation and differentiation. Accumulated evidences have demonstrated that deacetylation serves as a key modulator of the function of the genes predominantly expressed in SCs. We previously found that Metastasis associated protein 2 (MTA2), a recruiter of histone deacetylases, was exclusively expresssed in SCs.Its expression could be regulated by androgen pathway. MTA2 was involved in the homologous down-regulation of transcription of the FSH receptor gene in SCs. Furthermore, an attenuated expression patter of MTA2 was detected in pathological human testis with severe spermatogenic failure such as Sertoli cell only syndrome(SCOS), indicating a potential involvement of this histone modifier during the pathogenesis. These data collectively suggest that MTA2 may be an important regulator in SCs during spermatogenesis. An investigation is therefore to be initiated to futher study the potential relationship between MTA2, FSH-pathway and androgen signaling.We also try to observe the effect of ablation of MTA2 on the development and differentiatin

英文关键词： MTA2；Sertoli cell；deacetylation modification；transcriptional regulation；spermatogenesis