Apelin protects against acute renal injury by inhibiting TGF-β1

Biochim Biophys Acta. 2015 Jul;1852(7):1278-87. doi: 10.1016/j.bbadis.2015.02.013. Epub 2015 Mar 6.


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.

Keywords: Apelin; Histone methylation; Renal I/R injury; TGF-β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line
  • 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
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*


  • Histones
  • Intercellular Signaling Peptides and Proteins
  • Transforming Growth Factor beta1
  • apelin-13 peptide