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Klotho ameliorates sepsis-induced acute kidney injury but is irrelevant to autophagy

Authors Chen X, Tong H, Chen Y, Chen C, Ye J, Mo Q, Zhao G, Hong G, Zheng C, Lu Z

Received 14 November 2017

Accepted for publication 21 December 2017

Published 19 February 2018 Volume 2018:11 Pages 867—881

DOI https://doi.org/10.2147/OTT.S156891

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Xinxin Chen,1 Huan Tong,2 Yu Chen,3 Chaosheng Chen,1 Jingjing Ye,2 Qingfei Mo,2 Guangju Zhao,2 Guangliang Hong,2 Chenfei Zheng,1 Zhongqiu Lu2

1Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 2Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 3Department of Nephrology, Wenzhou Hospital of Traditional Chinese Medicine Affiliated with Zhejiang Chinese Medical University, Wenzhou, Zhejiang, China

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.

Keywords: acute kidney injury, autophagy, klotho, septic AKI, Rapamycin, 3-MA

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