Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation
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 fir...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Renal Failure |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/0886022X.2021.1915801 |
| _version_ | 1798031752002797568 |
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| author | A-Feng Miao Jian-Xiang Liang Lei Yao Jun-Ling Han Li-Juan Zhou |
| author_facet | A-Feng Miao Jian-Xiang Liang Lei Yao Jun-Ling Han Li-Juan Zhou |
| author_sort | A-Feng Miao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T20:02:38Z |
| format | Article |
| id | doaj.art-8df76aa9b91046918f003449faa18a7b |
| institution | Directory Open Access Journal |
| issn | 0886-022X 1525-6049 |
| language | English |
| last_indexed | 2024-04-11T20:02:38Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj.art-8df76aa9b91046918f003449faa18a7b2022-12-22T04:05:32ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492021-01-0143180381010.1080/0886022X.2021.19158011915801Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammationA-Feng Miao0Jian-Xiang Liang1Lei Yao2Jun-Ling Han3Li-Juan Zhou4Department of Nephrology, Taizhou People’s Hospital, Fifth Affiliated Hospital to Nantong UniversityDepartment of Ultrasonography, Weifang People's HospitalDepartment of Anesthesiology, Second Affiliated Hospital of Nantong UniversityClinical Laboratory, Taizhou People’s Hospital, Fifth Affiliated Hospital to Nantong UniversityDepartment of Nephrology, Taizhou People’s Hospital, Fifth Affiliated Hospital to Nantong UniversityHypoxia-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.http://dx.doi.org/10.1080/0886022X.2021.1915801fg-4592renal ischemia/reperfusion injuryinflammation |
| spellingShingle | A-Feng Miao Jian-Xiang Liang Lei Yao Jun-Ling Han Li-Juan Zhou Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation Renal Failure fg-4592 renal ischemia/reperfusion injury inflammation |
| title | Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation |
| title_full | Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation |
| title_fullStr | Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation |
| title_full_unstemmed | Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation |
| title_short | Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation |
| title_sort | hypoxia inducible factor prolyl hydroxylase inhibitor roxadustat fg 4592 protects against renal ischemia reperfusion injury by inhibiting inflammation |
| topic | fg-4592 renal ischemia/reperfusion injury inflammation |
| url | http://dx.doi.org/10.1080/0886022X.2021.1915801 |
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