Apelin protects against acute renal injury by inhibiting TGF-β1

• Published in: Biochimica et biophysica acta Vol. 1852; no. 7; pp. 1278 - 1287
• Main Authors: Chen, Hong, Wan, Danyang, Wang, Lin, Peng, Anlin, Xiao, Hongdou, Petersen, Robert B., Liu, Chengyu, Zheng, Ling, Huang, Kun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2015
• Subjects: Animals; Apelin; Apoptosis; Cell Line; Histone methylation; Histones - metabolism; Intercellular Signaling Peptides and Proteins - pharmacology; Intercellular Signaling Peptides and Proteins - therapeutic use; Kidney - blood supply; Kidney - drug effects; Kidney - metabolism; Male; Rats; Rats, Wistar; Renal I/R injury; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; TGF-β1; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; MCP-1; HDMs; HMTs; Histone methylation; H/R; ICAM-1; I/R; PARP-1; TGF-β1; HAT; ATN; 2K1C; AKI; HDAC; Apelin; Renal I/R injury
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2015.02.013

Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney injury, having a high rate of mortality and no effective therapy currently available. Apelin-13, a bioactive peptide, has been shown to inhibit the early lesions of diabetic nephropathy in several mouse models by us and others. To test whether apelin-13 protects against renal I/R induced injury, male rats were exposed to renal I/R injury with or without apelin-13 treatment for 3days. Apelin-13 treatment markedly reduced the injury-induced tubular lesions, renal cell apoptosis, and normalized the injury induced renal dysfunction. Apelin-13 treatment inhibited the injury-induced elevation of inflammatory factors and Tgf-β1, as well as apoptosis. Apelin-13 treatment also inhibited the injury-induced elevation of histone methylation and Kmt2d, a histone methyltransferase of H3K4me2, following renal I/R injury. Furthermore, in cultured renal mesangial and tubular cells, apelin-13 suppressed the injury-induced elevation of Tgf-β1, apoptosis, H3K4me2 and Kmt2d under the in vitro hypoxia/reperfusion (H/R) conditions. Consistently, over-expression of apelin significantly inhibited H/R-induced elevation of TGF-β1, apoptosis, H3K4me2 and Kmt2d. The present study therefore suggests apelin-13 may be a therapeutic candidate for treating acute kidney injury. •Apelin-13 attenuated the I/R injury-induced renal dysfunction.•Apelin-13 inhibited the I/R or H/R injury induced elevation of TGF-β1 in kidneys and in cultured renal cells.•Apelin-13 normalized the histone methylation levels after renal I/R injury or H/R injury in cultured renal cells