M2巨噬细胞通过TGFβ-RhoA/ROCK通路介导BMSCs定向归巢促进损伤血管再内皮化的机制研究

骨髓间充质干细胞（BMSCs）可归巢至血管损伤部位参与早期再内皮化，抑制腔内治疗后血栓及再狭窄形成，但其归巢机制目前尚不明确。TGF-β信号通路可介导BMSCs在肿瘤的定向归巢，我们预实验发现高表达TGF-β的M2巨噬细胞在损伤血管壁大量浸润且显著促进BMSCs的体外迁移。因此我们假设：M2巨噬细胞通过TGF-β/Smad介导RhoA/ROCK通路调控BMSCs定向归巢至血管损伤部位并促进再内皮化。在前期工作基础上，拟进一步研究体外、体内M2巨噬细胞对BMSCs粘附、迁移等的影响，通过基因过表达/沉默、RNA干扰探索TGF-β/Smad-RhoA/ROCK信号通路在该过程中的调控作用；并运用巨噬细胞清除、基因示踪、扫描电镜等研究M2巨噬细胞体内诱导BMSCs定向归巢促进小鼠颈动脉内皮损伤模型再内皮化的作用及机制，为防治腔内治疗术后血栓及再狭窄形成提供新思路及理论依据。

Bone marrow-derived stem cells (BMSCs) home to the injured site and participate in the re-endothelialization of arteries. However, the homing mechanism has not been clarified. It has been reported that TGF-β signaling mediates the homing of BMSCs to cancer stem cells (CSCs). In our preliminary study, M2 macrophages that highly express TGF-β promote the migration effect of BMSCs in vitro. Therefore, we hypothesize that M2 macrophages mediate the homing of BMSCs to injured arteries through TGF-β/Smad-RhoA/ROCK signal transduction and further promote re-endothelialization. Based on our previous work, in this study, we further investigate M2 macrophages on the homing of BMSCs in vitro and in vivo, and probe into the TGF-β/Smad-RhoA/ROCK signal transduction in mediating this process through gene overexpression/ knockdown and RNA interfering. Moreover, GFP gene was applied to trace the homing of BMSCs to M2 macrophages and re-endothelialization. This study would bring new insights into the prognosis and treatment of in-stent restenosis and thrombosis formation.