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

Autor: Pan Liu, Yiqing Li, Mengyao Li, Hui Zhou, Huilun Zhang, Yuefei Zhang, Jiaqi Xu, Yun Xu, Jie Zhang, Bing Xia, Hongqiang Cheng, Yuehai Ke, Xue Zhang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: iScience, Vol 25, Iss 3, Pp 103867- (2022)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2022.103867
Popis: Summary: Radiation-induced lung injury is a common late side effect of thoracic radiotherapy. Endothelial dysfunction following leukocytes infiltration is a prominent feature in this process. Here, we established a clinical-mimicking mouse model of radiation-induced lung injury and found the activity of phosphatase Shp2 was elevated in endothelium after injury. Endothelium-specific Shp2 deletion mice showed relieved collagen deposition along with disrupted radiation-induced Jag1 expression in the endothelium. Furthermore, endothelium-derived Jag1 activated the alternative activation of macrophages in vitro and in vivo by paracrine Notch signaling. Consistently, the Notch pathway was significantly activated by chest irradiation in the peripheral blood leukocytes of patients with cancer. Collectively, our work demonstrates that Shp2 participates in the radiation-induced endothelial dysfunction and subsequently inflammatory microenvironment producing during radiation-induced lung injury. Our findings indicate Shp2 as a potential target for radiation-induced lung injury and provide another way for endothelium to participate in the pathological process of radiation-induced lung injury.
Databáze: Directory of Open Access Journals