Fc-Elabela fusion protein attenuates lipopolysaccharide-induced kidney injury in mice
MetadataShow full item record
AbstractEndotoxemia-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 itemhttp://hdl.handle.net/10713/13674
- Recombinant Fc-Elabela fusion protein has extended plasma half-life andmitigates post-infarct heart dysfunction in rats.
- Authors: Xi Y, Yu D, Yang R, Zhao Q, Wang J, Zhang H, Qian K, Shi Z, Wang W, Brown R, Li Y, Tian Z, Gong DW
- Issue date: 2019 Oct 1
- Fc-apelin fusion protein attenuates lipopolysaccharide-induced liver injury in mice.
- Authors: Zhou H, Yang R, Wang W, Xu F, Xi Y, Brown RA, Zhang H, Shi L, Zhu D, Gong DW
- Issue date: 2018 Jul 30
- Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice.
- Authors: Ren Q, Guo F, Tao S, Huang R, Ma L, Fu P
- Issue date: 2020 Feb
- ELABELA antagonizes intrarenal renin-angiotensin system to lower blood pressure and protects against renal injury.
- Authors: Xu C, Wang F, Chen Y, Xie S, Sng D, Reversade B, Yang T
- Issue date: 2020 May 1
- ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway.
- Authors: Chen Z, Wu C, Liu Y, Li H, Zhu Y, Huang C, Lin H, Qiao Q, Huang M, Zhu Q, Wang L
- Issue date: 2020 Aug 22