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      Hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat (FG-4592) alleviates sepsis-induced acute lung injury.

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          Abstract

          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.

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          Author and article information

          Journal
          Respir Physiol Neurobiol
          Respiratory physiology & neurobiology
          Elsevier BV
          1878-1519
          1569-9048
          October 2020
          : 281
          Affiliations
          [1 ] Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, China.
          [2 ] Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, China. Electronic address: hanjt@fmmu.edu.cn.
          [3 ] Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, China. Electronic address: hudahaidoc@163.com.
          Article
          S1569-9048(20)30164-6
          10.1016/j.resp.2020.103506
          32726645

          Sepsis, ALI, HIF-1α, Inflammation, FG-4592(Roxadustat)

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