Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through Notch signaling

Our findings demonstrate that endothelial Shp2 is a key regulator in radiation-induced lung injury by maintaining the radiation-induced Jag1 level through the β-catenin pathway, thereby reducing alternative macrophage activation to relieve radiation-induced lung injury. Two short-term and a long-term mouse model were used to evaluate the role of endothelial Shp2 in radiation-induced lung injury. The in vitro co-culture system was used to investigate the relationship between irradiated-endothelium and macrophage. HUVECs and MLECs were used here for in vitro study.

本研究结果显示，内皮细胞Shp2（endothelial Shp2）是辐射诱导肺损伤的关键调控因子，其通过β-连环蛋白（β-catenin）通路维持辐射诱导的Jag1蛋白（Jag1）水平，进而抑制替代性巨噬细胞活化以减轻辐射诱导肺损伤。本研究采用两种小鼠模型，分别为短期模型与长期模型，以评估内皮细胞Shp2在辐射诱导肺损伤中的调控作用。同时，本研究通过体外共培养体系，探究辐照内皮细胞与巨噬细胞间的相互作用关系。本次体外实验选用了人脐静脉内皮细胞（Human Umbilical Vein Endothelial Cells，HUVECs）与小鼠肺微血管内皮细胞（Mouse Lung Microvascular Endothelial Cells，MLECs）作为实验材料。