Endoglin（ENG）是TGF-β共受体。ENG基因突变导致1型遗传性出血性毛细血管扩张症（HHT）并引起脑卒中。ENG参与炎性反应, 但机制不明。我们研究显示，Eng+/-鼠脑缺血急性期的CD68+细胞表达减少，恢复期仍有明显表达，且脑损伤更严重。提示ENG基因缺陷导致损伤加剧与炎性细胞浸润相关。研究表明脑缺血后早期小胶质细胞以M2型浸润为主，有保护作用。M1型则加剧脑损伤。在内皮细胞上，ENG通过TGF-β及其I型受体ALK1和ALK5传递信号。据此推测ENG基因缺陷可能促使激活的小胶质细胞向M1型转化，与TGF-β/ALK/Smad信号通路有关。本研究拟用Eng+/-小鼠，通过大脑中动脉缺血模型和细胞共培养系统等相关实验技术，研究脑缺血后小胶质细胞分型，揭示ENG基因通过TGF-β/ALK/Smad信号通路来调节小胶质细胞功能的机制。有助于阐明HHT及其所致脑卒中的发病机制。

Endoglin is a transmembrane protein and an auxiliary receptor for TGF-β. Mutations in Endoglin cause type 1 hereditary hemorrhagic telangiectasia (HHT1), which causes stroke. Endoglin is involved in inflammatory response, but the mechanism is unknown. Our data indicated that compared to WT mice, Eng+/− mice had fewer CD68+ microphages at acute stage and more CD68+ macrophages at the post-acute stage of ischemic stroke, and impairs brain ischemic injury repair, which indicated that Eng-deficiency impairs macrophage homing to the injury site. Soon after an ischemic injury, a majority of microglia/macrophages migrating or infiltrating into the infarct areas initially assume the M2 phenotype which helps to reduce brain injury. M1 exacerbate ischemic injury. Endoglin modulate the activities of TGF-β/ALK signaling in endothelia cells. Both TGF-β and ALK are expressed by macrophages. We hypotheses that TGF-β/ ALK /Smad signal involved in the impaired microglia homing and polarization caused by Eng-deficiency. In this study, we will use Eng+/- mice, middle cerebral artery occlusion model as well as microglia transwell co- culture system, and with a variety of experimental techniques, to explore the association of macrophage homing and differentiation in Endoglin deficiency mice, and to invastigate whether Endoglin regulate microglia polarization through TGF-β/ALK /Smad signaling pathways. This will help to clarify the pathogenesis of HHT and related cerebral vascular disease.