申请人前期研究表明，Lrrc10通过抑制SRF信号来抑制心肌肥大发生。申请人课题组和国际同行最新研究进展提示，成体心脏高表达基因很可能是自主抑制心肌肥大发生的始发性因子；成体心脏高表达基因Lrrc10很可能还存在另一种通过心肌结构蛋白来抑制心肌肥大发生的分子调控机制。在酵母双杂交筛选得到lrrc10相互作用心肌结构蛋白 desmin的基础上，本项目拟采用细胞模型、双基因敲除与双转基因小鼠模型及人类样本，通过Western blot、Co-IP、EMSA、CHIP等多种实验方法，研究lrrc10与desmin是否协同抑制心肌细胞肥大表型发生，两者间分子相互作用关系,lrrc10是否desmin上游转录调控因子，及lrrc10与desmin协同调控心肌肥大发生的分子机制。该项目对探讨心肌肥大发生的理论机制，发现治疗人类心肌肥大的新方法具有重要意义，很可能形成具有原创性知识产权的理论和技术成果。

Our previous studies proved that lrrc10 gene acts as a SRF signaling pathway- mediated protective molecular in cardiac hypertrophy. Our recent results and international progess suggested highly-expressed molecules maybe that of the first line of defense with cardiac hypertrophy, and the highly-expressed LRRC10 gene in adult heart gene may have another molecular inhibition mechamism on cardiac hypertrophy through cardiac structual proteins. As a result, we screened a new target gene of lrrc10 gene named desmin using two hybrid system, which is also a highly-expressed structual protein in heart tissue. In this project,using the materials and methods including double transgenic and knock out mouse models,human primary cardiac hypertrophy tissues, western blot, Real-time PCR, Co-IP, EMSA, etc.,we plan to study the molecular mechanism of synergistic repression on cardiac hypertrophy by two highly cardiac-expressed genes lrrc10 and desmin. This application has obvious significances on finding novel and useful therapeutic targets for cardiac hypertrophy. It will be possible to form a series of original theory and technique results.