ELABELA and an ELABELA Fragment Protect against AKI.

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.

• Authors: Hong Chen, Lin Wang, Wenjun Wang, Cheng Cheng, Yu Zhang, Yu Zhou, Congyi Wang, Xiaoping Miao, Jiao Wang, Chao Wang, Jianshuang Li, Ling Zheng, Kun Huang
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 28 Issue 9 Pg. 2694-2707 (Sep 2017) ISSN: 1533-3450 [Electronic] United States
• PMID: 28583915 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 by the American Society of Nephrology.

Chemical References

• APELA protein, human
• Apela protein, mouse
• Carrier Proteins
• Cell Adhesion Molecules
• Havcr1 protein, mouse
• Havcr1protein, rat
• Hepatitis A Virus Cellular Receptor 1
• Histones
• ICAM1 protein, rat
• Interleukin-6
• Peptide Fragments
• Peptide Hormones
• Phosphoproteins
• RNA, Messenger
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• gamma-H2AX protein, rat
• Intercellular Adhesion Molecule-1
• ataxia telangiectasia and Rad3-related kinase, rat
• Ataxia Telangiectasia Mutated Proteins
• Checkpoint Kinase 1

Topics

• Acute Kidney Injury (genetics, metabolism, physiopathology, prevention & control)
• Animals
• Apoptosis (drug effects)
• Ataxia Telangiectasia Mutated Proteins (metabolism)
• Autophagy (drug effects)
• Carrier Proteins (genetics, pharmacology, 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, prevention & control)
• Intercellular Adhesion Molecule-1 (genetics)
• Interleukin-6 (genetics)
• Kidney Tubules (cytology)
• Mice
• Peptide Fragments (genetics, pharmacology, therapeutic use)
• Peptide Hormones (pharmacology, therapeutic use)
• Phosphoproteins (metabolism)
• Phosphorylation
• RNA, Messenger (metabolism)
• Rats
• Reperfusion Injury (genetics, metabolism, physiopathology, prevention & control)
• Transforming Growth Factor beta1 (genetics)
• Tumor Necrosis Factor-alpha (genetics)