ELABELA and an ELABELA Fragment Protect against AKI

• Published in: Journal of the American Society of Nephrology 2017-09, Vol.28 (9), p.2694-2707
• Main Authors: Chen, Hong, Wang, Lin, Wang, Wenjun, Cheng, Cheng, Zhang, Yu, Zhou, Yu, Wang, Congyi, Miao, Xiaoping, Wang, Jiao, Wang, Chao, Li, Jianshuang, Zheng, Ling, Huang, Kun
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - genetics; Acute Kidney Injury - metabolism; Acute Kidney Injury - physiopathology; Acute Kidney Injury - prevention & control; Animals; Apoptosis - drug effects; Ataxia Telangiectasia Mutated Proteins - metabolism; Autophagy - drug effects; Basic Research; Carrier Proteins - genetics; Carrier Proteins - pharmacology; Carrier Proteins - therapeutic use; Cell Adhesion Molecules - genetics; Cell Hypoxia; Cell Line; Cell Survival - drug effects; Checkpoint Kinase 1 - metabolism; DNA Repair - drug effects; Gene Expression - drug effects; Hepatitis A Virus Cellular Receptor 1 - genetics; Histones - metabolism; Humans; Inflammation - genetics; Inflammation - prevention & control; Intercellular Adhesion Molecule-1 - genetics; Interleukin-6 - genetics; Kidney Tubules - cytology; Mice; Peptide Fragments - genetics; Peptide Fragments - pharmacology; Peptide Fragments - therapeutic use; Peptide Hormones - pharmacology; Peptide Hormones - therapeutic use; Phosphoproteins - metabolism; Phosphorylation; Rats; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Reperfusion Injury - prevention & control; RNA, Messenger - metabolism; Transforming Growth Factor beta1 - genetics; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2016111210

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 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.