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J Am Soc Nephrol. 2017 Sep;28(9):2694-2707. doi: 10.1681/ASN.2016111210. Epub 2017 Jun 5.

ELABELA and an ELABELA Fragment Protect against AKI.

Author information

1
Tongji School of Pharmacy.
2
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China; and.
3
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri.
4
The Center for Biomedical Research, Tongji Hospital, and.
5
School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
6
Tongji School of Pharmacy, kunhuang2008@hotmail.com.

Abstract

Renal ischemia-reperfusion (I/R) injury is the most common cause of AKI, which associates with high mortality and has no effective therapy. ELABELA (ELA) is a newly identified 32-residue hormone peptide highly expressed in adult kidney. To investigate whether ELA has protective effects on renal I/R injury, we administered the mature peptide (ELA32) or the 11-residue furin-cleaved fragment (ELA11) to hypoxia-reperfusion (H/R)-injured or adriamycin-treated renal tubular cells in vitro ELA32 and ELA11 significantly inhibited the elevation of the DNA damage response, apoptosis, and inflammation in H/R-injured renal tubular cells and suppressed adriamycin-induced DNA damage response. Similarly, overexpression of ELA32 or ELA11 significantly inhibited H/R-induced cell death, DNA damage response, and inflammation. Notably, treatment of mice with ELA32 or ELA11 but not an ELA11 mutant with a cysteine to alanine substitution at the N terminus (AE11C) inhibited I/R injury-induced renal fibrosis, inflammation, apoptosis, and the DNA damage response and markedly reduced the renal tubular lesions and renal dysfunction. Together, our results suggest that ELA32 and ELA11 may be therapeutic candidates for treating AKI.

KEYWORDS:

DNA damage response; ELABELA; acute kidney injury; inflammation

PMID:
28583915
PMCID:
PMC5576937
DOI:
10.1681/ASN.2016111210
[Indexed for MEDLINE]
Free PMC Article

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