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.

本研究结果表明，内皮细胞Shp2是放射性肺损伤的关键调控因子：其可通过β-连环蛋白通路维持辐照诱导的Jag1水平，进而抑制替代性巨噬细胞活化，从而缓解放射性肺损伤。本研究采用两种短期小鼠模型与一种长期小鼠模型，用以评估内皮细胞Shp2在放射性肺损伤中的调控作用；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，并选用人脐静脉内皮细胞（Human Umbilical Vein Endothelial Cells, HUVECs）与小鼠肺微血管内皮细胞（Mouse Lung Microvascular Endothelial Cells, MLECs）开展体外实验。