ci-Eln促进亲本基因Eln介导的缺氧肺动脉平滑肌细胞增殖的机制研究

目前认为肺动脉平滑肌细胞（PASMCs）增殖失衡是诱发缺氧性脉高压（HPH）重要的病理基础，但其调控机制尚不能完全明确，circRNA与PASMCs增殖密切相关，但位于胞核内的circRNA是否参与PASMCs增殖尚未见任何报道。我们的前期探索发现，在缺氧性PAH中首次鉴定出67个新的circRNA的表达水平发生显著改变。其中位于胞核内的ci-Eln的表达上调并参与PASMCs增殖，调控RNA聚合酶Ⅱ（RNA polⅡ）及弹性蛋白基因Eln的表达。我们假设ci-Eln通过RNA polⅡ及Eln调控肺动脉高压中的PASMCs增殖。为了证实这一假设将解决：ci-Eln自身的特性；其在PASMCs增殖中所扮演的角色是什么；ci-Eln通过何种机制调控PASMCs增殖和肺血管重构。这些问题的解决将为PAH的临床治疗提供重要的理论基础和全新的思路。

Recent studies suggest that the imbalance of proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important pathological basis of hypoxia-induced arterial hypertension (HPH) , however, its specific regulatory mechanism is not clear. CircRNAs are closely related to the proliferation of PASMCs, but the involvement of circRNA that Positioning in the nucleus in the proliferation of PASMCs has not been reported. Our previous research found that for the first time in anoxic PAH, 67 new circRNAs expression level changed significantly. Among them, the expression of ci-Eln in nucleus was up-regulated and involved in the proliferation of PASMCs, which regulating the expression of RNA Polymerase II (RNA polII) and elastine Eln. We hypothesized that ci-Eln regulated the proliferation of PASMCs in pulmonary hypertension through RNA polII and Eln. We will solve the following questions: the characteristics of ci-Eln themselves; What is its role in the proliferation of PASMCs; What are the mechanisms by which ci-Eln regulate the proliferation and pulmonary vascular remodeling of PASMCs. The solution of these problems will provide an important theoretical basis and a new idea for the clinical treatment of PAH.