Fu Han 1 , Gaofeng Wu 1 , Shichao Han 1 , Zhenzhen Li 1 , Yanhui Jia 1 , Lu Bai 1 , Xiaoqiang Li 1 , Kejia Wang 1 , Fangfang Yang 1 , Jian Zhang 1 , Xujie Wang 1 , Hao Guan 1 , Su Linlin 1 , Juntao Han 2 , Dahai Hu 3
Acute lung injury (ALI) is one of the most severe outcomes of sepsis which still waiting for effective treatment method. Roxadustat (FG-4592) which is often used for treatment of anemia in patients with chronic kidney disease (CKD), its affection on LPS-induced ALI haven't been evaluated. MH-S and MLE-12 cell injury and ALI mouse model was induced LPS. Several assays were used to explore the role of FG-4592 in reducing the damage caused by LPS. FG-4592 treatment significantly upregulated HIF-1α and HO-1 and strikingly attenuated inflammation in vivo and in vitro. Furthermore, septic mice overexpressing HIF-1α had high level of survival rate and lower expression of inflammatory factors while down-regulation can enhance the damage of LPS. HIF-1α has a protective effect on acute lung injury in LPS induced septic mice. FG-4592 treatment remarkably ameliorated the LPS-induced lung injury through the stabilization of HIF-1α. Besides the role in treating CKD anemia, the clinical use of FG-4592 also might be extended to ALI.