Apelin protects against acute renal injury by inhibiting TGF-β1.
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 3 days. 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.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China, 430030; Centre for Biomedicine Research, Wuhan Institute of Biotechnology, Wuhan, China, 430074.
Hong
H
Chen
College of Life Sciences, Wuhan University, Wuhan, China, 430072.
Danyang
D
Wan
College of Life Sciences, Wuhan University, Wuhan, China, 430072.
Lin
L
Wang
Wuhan the Third Hospital, Wuhan, China, 430060.
Anlin
A
Peng
College of Life Sciences, Wuhan University, Wuhan, China, 430072.
Hongdou
H
Xiao
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA, 44106; Department of Neuroscience, Case Western Reserve University, Cleveland, OH, USA, 44106; Department of Neurology, Case Western Reserve University, Cleveland, OH, USA, 44106.
Robert B
RB
Petersen
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China, 430030; Centre for Biomedicine Research, Wuhan Institute of Biotechnology, Wuhan, China, 430074.
Chengyu
C
Liu
College of Life Sciences, Wuhan University, Wuhan, China, 430072. Electronic address: lzheng217@hotmail.com.
Ling
L
Zheng
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China, 430030; Centre for Biomedicine Research, Wuhan Institute of Biotechnology, Wuhan, China, 430074. Electronic address: kunhuang2008@hotmail.com.
Kun
K
Huang
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D006657:Histones / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D053773:Transforming Growth Factor beta1; C495199:apelin-13 peptide
Apelin; Histone methylation; Renal I/R injury; TGF-β1