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- Title
Klotho ameliorates sepsis-induced acute kidney injury but is irrelevant to autophagy.
- Authors
Chen, Xinxin; Tong, Huan; Chen, Yu; Chen, Chaosheng; Ye, Jingjing; Mo, Qingfei; Zhao, Guangju; Hong, Guangliang; Zheng, Chenfei; Lu, Zhongqiu
- Abstract
Background: The role of Klotho (KL) in sepsis-induced acute kidney injury (AKI) and the potential relationship between KL and autophagy in septic AKI were investigated. Materials and methods: A murine model of sepsis-induced AKI was established by cecal ligation and puncture (CLP). Mice undergoing CLP and immortalized proximal tubular epithelial human HK-2 cells that were exposed to lipopolysaccharide (LPS) were treated with recombinant KL, autophagy stimulator rapamycin (Rap), and autophagy suppressor 3-methyladenine (3-MA). Results: Autophagy activation and KL reduction reached maximum levels in mice 24 hours after CLP. Recombinant KL and/or Rap significantly attenuated CLP-induced renal dysfunction (P<0.05) and partially restored endogenous renal KL expression (P<0.05). Recombinant KL had no impact on CLP-induced autophagy and apoptosis, whereas Rap significantly stimulated autophagy and reduced apoptosis in mice. 3-MA significantly exacerbated renal dysfunction, increased apoptosis, and inhibited autophagy in mice with CLP-induced AKI (all P<0.05). In LPS-treated HK-2 cells, Rap significantly enhanced autophagy and reduced apoptosis (all P<0.05), whereas recombinant KL had no impact, and 3-MA inhibited autophagy and significantly increased apoptosis (P<0.05). Conclusion: Recombinant KL alleviates renal dysfunction and restores renal KL expression in mice with sepsis-induced AKI, but the underlying mechanism may not be related to autophagy induction.
- Subjects
KIDNEY injuries; CLOTHO (Greek deity); AUTOPHAGY; RAPAMYCIN; GENE expression
- Publication
OncoTargets & Therapy, 2018, Vol 11, p867
- ISSN
1178-6930
- Publication type
Article
- DOI
10.2147/OTT.S156891