Fc-Elabela fusion protein attenuates lipopolysaccharide-induced kidney injury in mice
Author
Xu, FengZhou, Huifen
Wu, Man
Zhang, Hong
Zhang, Yixian
Zhao, Qingbin
Brown, Robert
Gong, Da-Wei
Miao, Lining
Date
2020-09-30Journal
Bioscience ReportsPublisher
Springer NatureType
Article
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Endotoxemia-induced acute kidney injury (AKI) is a common clinical condition that lacks effective treatments. Elabela (ELA) is a recently discovered kidney peptide hormone, encoded by the gene apela, and has been reported to improve cardio-renal outcomes in sepsis. However, ELA is a small peptide and is largely unsuitable for clinical use because of its short in vivo half-life. In the present study, we evaluated the potential renoprotective effects of a long-acting constant fragment (Fc)-ELA fusion protein in liposaccharide (LPS)-induced AKI in mice. LPS administration in mice for 5 days greatly lowered the gene expression of apela and impaired kidney function, as evidenced by elevated serum creatinine and the ratio of urine protein to creatinine. In addition, renal inflammation and macrophage infiltration were apparent in LPS-challenged mice. Treatment with the Fc-ELA fusion protein partially restored apela expression and attenuated the kidney inflammation. Moreover, LPS treatment induced reactive oxygen species (ROS) production and apoptosis in kidney HK-2 cells as well as in the mouse kidney, which were mitigated by ELA or Fc-ELA treatment. Finally, we found that ELA promoted the survival of HK-2 cells treated with LPS, and this action was abolished by LY204002, a PI3K/Akt inhibitor. Collectively, we have demonstrated that the Fc-ELA fusion protein has significant renoprotective activities against LPS-induced AKI in mice.Rights/Terms
© 2020 The Author(s).Identifier to cite or link to this item
http://hdl.handle.net/10713/13674ae974a485f413a2113503eed53cd6c53
10.1042/BSR20192397
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