TY - JOUR
T1 - Apelin protects against acute renal injury by inhibiting TGF-β1
AU - Chen, Hong
AU - Wan, Danyang
AU - Wang, Lin
AU - Peng, Anlin
AU - Xiao, Hongdou
AU - Petersen, Robert B.
AU - Liu, Chengyu
AU - Zheng, Ling
AU - Huang, Kun
N1 - Funding Information:
We thank Dr. Takakura (Osaka University) for apelin plasmid. This work was supported by the National Basic Research Program of China ( 2012CB524901 ), the Natural Science Foundation of China (Nos. 81202557 , 31271370 , 81172971 , 81222043 and 31471208 ), Central University Basic Research Funds (to L.Z.), the Municipal Key Technology Program of Wuhan ( Wuhan Bureau of Science & Technology , No. 201260523174 ), the Health Bureau of Wuhan ( WX12B06 ) and the Natural Science Foundation of Hubei Province ( 2013CFB359 and 2014CF021 ).
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - Apelin
KW - Histone methylation
KW - Renal I/R injury
KW - TGF-β1
UR - http://www.scopus.com/inward/record.url?scp=84938587497&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2015.02.013
DO - 10.1016/j.bbadis.2015.02.013
M3 - Article
C2 - 25748499
AN - SCOPUS:84938587497
VL - 1852
SP - 1278
EP - 1287
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 7
ER -