hnRNPA1对血管平滑肌细胞分化和表型转换及损伤诱导的内膜新生的作用及机制研究

血管壁干/祖细胞向平滑肌细胞（SMCs）分化及成熟SMCs的表型转化均参与血管损伤后修复及病理性重塑过程。如果能找到一种分子，即能促进血管壁干细胞分化为收缩型的SMCs，又能维持成熟SMCs的收缩表型、抑制其发生表型转化，有可能成为有效防治动脉粥样硬化、再狭窄等血管疾病的理想方法。我们已经发现hnRNPA1能促进胚胎干细胞分化为SMCs，近期预实验结果显示hnRNPA1还能调控SMCs表型转化。本项目拟研究：1. hnRNPA1在血管壁干/祖细胞向SMCs分化中的作用及其对分化来的SMCs功能的影响；2. hnRNPA1对成熟SMCs表型转化后增殖、迁移功能的影响及其分子机制；3. hnRNPA1对小鼠颈动脉导丝损伤后内膜新生的作用；4. hnRNPA1对血管损伤后内膜新生的影响是否通过调控干/祖细胞分化和/或SMCs表型转化来实现；5. 人体病变血管及正常血管中hnRNPA1的表达差异。

Both adventitial stem/progenitor cell differentiation into vascular smooth muscle cells and vascular smooth muscle cell phenotypic switching participate in vascular injury, repair and pathological remolding. A molecule that can promotes stem/progenitor cell dfferentiation into smooth muscle cells and inhibit mature smooth muscle cell phenotypic modulation after vascular injury might be a promising therapy for cardiovascular disorders, such as atherosclerosis and restenosis. we have revealed the involvement of hnRNPA1 in smooth muscle cell differentiation from embryonic stem cells. In this project, we will investigate: 1.Whether hnRNPA1 can promote stem/progenitor cell differentiation into functional mature smooth muscle cells. 2.Whether hnRNPA1 can modulate smooth muscle cell phenotype by repressing its proliferation and migration, and its underlying mechanisms. 3.Whether hnRNPA1 affects injury-induced carotid artery neointima formation. 4.How hnRNPA1 controls neointima formation through regulating stem/progenitor cell differentiation and/or smooth muscle cell phenotypic switching. 5.hnRNPA1 expression in human normal and diseased arteries.