血管平滑肌细胞（VSMC）过度增殖是动脉粥样硬化（AS）的主要致病因素，lncRNA在其中的调控机制尚未阐明。本课题组前期发现，lnc-ITGA1-1在增殖的人VSMCs和AS组织中表达升高，敲减lnc-ITGA1-1后可抑制VSMC增殖和迁移，同时抑制了整合素α2（ITGA2）的表达水平及其下游信号的活化。因此，本课题拟针对lnc-ITGA1-1在转录及转录后水平调控ITGA2的表达展开研究。运用ChIRP和ChIP等手段明确胞核lnc-ITGA1-1对ITGA2启动子区表观修饰及基因转录活性的调控作用；利用RNA-pull down和Deletion Mapping等技术阐明胞质内lnc-ITGA1-1与ITGA2蛋白的结合位点、检测其对ITGA2蛋白稳定性以及对下游信号通路活性的影响；从而系统探索lnc-ITGA1-1对VSMC过度增殖和迁移的调控机制，为AS的靶向治疗提供新思路。

Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute significantly to the development of vascular pathologies, such as atherosclerosis and restenosis. Long noncoding RNAs (LncRNAs) have emerged as important regulators for VSMC function, however, the molecular mechanisms still remain unclear. We recently identified lnc-ITGA1-1 as critical for controlling human aortic smooth muscle cell (hAoSMCs) proliferation and migration. By using quantitative reverse-transcription polymerase chain reaction, we found that lnc-ITGA1-1 was significantly downregulated in hAoSMCs on platelet-derived growth factor (PDGF) treatment, whereas expression was markedly increased during VSMC differentiation. Furthermore, we demonstrated that knock down of lnc-ITGA1-1 increased expression of VSMC differentiation marker genes, such as smooth muscle 22α, smooth muscle α-actin, calponin, and smooth muscle myosin heavy chain, and potently inhibited PDGF-induced VSMC proliferation and migration. Therefore, the aim of this study is to clarify the role of lnc-ITGA1-1 in regulating integrin α2（ITGA2）in nucleus and cytoplasm. On the one hand, ChIRP and ChIP were used to explore the epigenetic modifications of promoter region of lnc-ITGA1-1 in the nucleus; on the other hand, combined with RNA-pull down and Deletion Mapping, the aim of this study was to explore the effects of lnc-ITGA1-1 in cytoplasm on the stability and downstream signal pathway activity of ITGA2 protein. Overall, the mechanism of lnc-ITGA1-1 in VSMC proliferation and migration will be systematically verified in the present study, which provides a new evidence for the targeted treatment of atherosclerosis (AS).