Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation |
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Authors: | A-Feng Miao Jian-Xiang Liang Lei Yao Jun-Ling Han Li-Juan Zhou |
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Affiliation: | aDepartment of Nephrology, Taizhou People’s Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu, China;bDepartment of Ultrasonography, Weifang People''s Hospital, Weifang, Shandong, China;cDepartment of Anesthesiology, Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China;dClinical Laboratory, Taizhou People’s Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu, China |
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Abstract: | Hypoxia-induced inflammation is the critical pathological feature of acute kidney injury (AKI). Activation of hypoxia-inducible factor (HIF) signaling is considered as a central mechanism of body adapting to hypoxia. Hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 (Roxadustat) is a first-in-class HIF stabilizer for the treatment of patients with renal anemia. The current study aimed to investigate whether FG-4592 could protect against ischemia/reperfusion (I/R)-induced kidney injury via inhibiting inflammation. Here, efficacy of FG-4592 was evaluated in a mice model of I/R-induced AKI. Interestingly, improved renal function and renal tubular injuries, combined with reduced kidney injury molecule-1 were observed in the mice with FG-4592 administration. Meanwhile, inflammation responses in FG-4592-treated mice were also strikingly attenuated, as evidenced by the decreased infiltration of macrophages and neutrophils and down-regulated expression of inflammatory cytokines. In vitro, FG-4592 treatment significantly protected the tubular epithelial cells against hypoxia-induced injury, with suppressed inflammation and cell injuries. In summary, FG-4592 treatment could protect against the I/R-induced kidney injury possibly through diminishing tubular cells injuries and suppression of sequence inflammatory responses. Thus, our findings definitely offered a clinical potential approach in treating AKI. |
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Keywords: | FG-4592 renal ischemia/reperfusion injury inflammation |
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