内皮细胞中p110γPI3K介导骨髓祖细胞对肺损伤修复作用及机制研究

Adult stem/progenitor cells treatment, which has shown to induce pulmonary vascular endothelial cell repair via paracrine mechanisms, is a potential novel therapeutic approach for acute lung injury, while the endogenous mediators in the pulmonary vasculature remain unclear. We have recently observed that bone marrow progenitor cell(BMPC)-induced vascular repair was abrogated in p110γ knock out mice following lung injury, which indicated that p110γ is required for the protective effect of BMPC. This project will further explore the role and molecular mechanisms of p110γ in mediating BMPC induced vascular repair of lung injury. The p110γ knock out mice will be used to investigate the role of p110γ in mediating BMPC-induced vascular repair of lung injury. In vitro, we will utilize siRNA to treat human pulmonary vascular endothelial cells or will isolate primary mouse pulmonary vascular endothelial cells to investigate the pivotal role of p110γ in mediating BMPC-induced vascular repair of lung injury and further identify the underlying mechanisms. The aim of this project is to clarify the role and mechanisms of p110γ in mediating BMPC-induced vascular of lung injury, which should provide an experimental base and new therapeutic target for the treatment of acute lung injury and acute respiratory distress syndrome.

干/祖细胞治疗被认为是急性肺损伤治疗中一种新型治疗方式，可以通过旁分泌作用促进肺血管内皮细胞的修复，但肺血管内皮细胞对干/祖细胞修复作用的介导机制目前还不是十分明确。我们近期的实验结果表明，在p110γ基因敲除小鼠中，骨髓祖细胞对肺血管损伤的修复作用受到明显的抑制，提示p110γ可能是介导骨髓祖细胞修复的关键因子。因此，本课题拟在此基础上进一步从体内外模型探讨p110γ对骨髓祖细胞修复作用的介导作用及其分子机制。体内研究拟利用p110γ敲除小鼠构建急性肺损伤模型来观察p110γ对骨髓祖细胞修复肺血管损伤的介导作用。体外实验拟利用人原代肺血管内皮细胞或提取p110γ敲除的小鼠原代肺血管内皮细胞，以进一步阐明p110γ对骨髓祖细胞修复肺血管损伤的介导机制。本课题旨在阐明肺血管内皮细胞中p110γ对骨髓祖细胞修复肺血管损伤的介导作用及机制，为急性肺损伤的治疗提供新靶点和重要的理论依据。