LncRNA Snhg5 在心脏重塑中功能和机制的研究

近年来的研究表明lncRNA在心脏疾病发生过程中发挥重要作用，有望成为心脏疾病重要的血清学诊断分子标志物及新型治疗靶标分子。我们前期对病理性心脏重塑小鼠模型进行RNA-seq检测时，发现Snhg5在心脏疾病组织中表达水平显著升高，体内外实验显示Snhg5能显著促进心肌肥厚的发生，表明其在心脏重塑过程中发挥一定的重要功能。为进一步揭示Snhg5在心脏重塑过程中发挥的功能及相应的作用机制，本研究拟首先确认Snhg5对心肌细胞生物学功能的影响，并探索其发挥功能的分子机制。通过研制心肌细胞特异性Snhg5过表达和敲除的遗传修饰小鼠，揭示Snhg5在体内维持心脏稳态的生理功能。本项目还将通过在经典的病理性心室重塑小鼠模型上抑制Snhg5的表达来评估其作为心脏疾病预防和治疗靶标的可能性。该研究将为心脏疾病发病机制研究提供新的表观遗传学理论，为心脏疾病的预防与治疗提供新型靶标分子。

Recent studies have shown that LncRNAs play important role in cardiac diseases, which could act as the vital biomarker for serological diagnosis of cardiac diseases and the new therapeutic target for treatment of heart disease. When screening the altered genes in pathogical cardiac remodeling by RNA-seq, we found that Snhg5 was significantly upregulated in the remodeling heart tissue and induce cardiac hypertrophy both in vitro and in vivo, suggesting that it must play an important role in the process of cardiac remodeling. To further reveal the function and the underlying mechanism of Snhg5 in maintaining cardiac homeostasis, we would verify the effect of Snhg5 on biological function of cardiomyocyte and explore the underlying mechanism. The cardiomyocyte-specific Snhg5 overexpression transgenic mice and Snhg5 knock out mice would be generated to reveal the physiological function of Snhg5 in cardiac homeostasis maintanence. Ultimately, the preventive and therapeutic effect of Snhg5 on cardiac disease would be evaluated by inhibition of Snhg5 expression in a mouse model of pathological cardiac remodeling. The project would advance the epigenetic theory in study of heart disease, and provide new preventative and therapeutic target for heart diseases.