骨骼肌损伤纤维化中差异表达LncRNA的筛选及其功能与机制研究

骨骼肌损伤后纤维化是制约损伤骨骼肌修复的关键因素，损伤骨骼肌纤维化的机制研究是探讨促进骨骼肌功能康复的重要方向。课题组既往研究证实了TGF-β/Smads等信号通路以及其与相关microRNA的复杂相互作用在损伤骨骼肌中发挥了重要作用。为探讨更上游的调控机制，在表观遗传、转录及转录后多个层面均可发挥明显调控作用的LncRNA，引起了我们的关注。本研究拟筛选并验证骨骼肌纤维化中显著差异表达的目标LncRNA；以过表达和敲减载体对目标LncRNA在纤维化中的功能进行验证；根据生物信息分析及数据库预测，并结合RNA pulldown、RIP等方法明确其作用靶点及其作用方式；再进一步探究对TGF-β/Smads等纤维化关键通路的调节作用与机制。最终明确LncRNA调控骨骼肌纤维化的具体功能及作用机制，从而为新的治疗方法提供思路和科学依据。

Skeletal muscle fibrosis after injury is a key factor limiting the healing of injured skeletal muscle. In order to facilitate the rehabilitation following skeletal muscle injury, the research in the mechanism of skeletal muscle fibrosis is of vital importance. Our previous studies have confirmed that TGF-β / Smads and other signaling pathways and their complex interactions with related microRNAs play an important role in the skeletal muscle fibrosis. In order to explore more upstream regulatory mechanisms, LncRNA, which plays a significant regulatory role at different levels, including epigenetics, transcription and post-transcription, has aroused our concern. In this study, LncRNA microarray is used to identify LncRNAs significantly differentially expressed during the process of skeletal muscle fibrosis. The function of target LncRNAs in fibrosis will be verified by constructing and transferring overexpression and knockdown vectors. According to bioinformatics analysis and database prediction, combined with results of RNA Pulldown, RIP and other methods, we will identify the target of LncRNA and clarify its mechanism of action. Then we will further explore the role and mechanism of target LncRNAs in the regulation of fibrosis-related pathways, and finally illuminate the function of LncRNAs in skeletal muscle fibrosis and its specific mechanisms, hence providing novel ideas and scientific basis for possible new treatments.