TY - JOUR
T1 - Apelin inhibits the development of diabetic nephropathy by regulating histone acetylation in Akita mouse
AU - Chen, Hong
AU - Li, Jianshuang
AU - Jiao, Lihua
AU - Petersen, Robert B.
AU - Li, Jiong
AU - Peng, Anlin
AU - Zheng, Ling
AU - Huang, Kun
PY - 2014/2
Y1 - 2014/2
N2 - Diabetic nephropathy is the primary cause of end-stage renal disease. Increasing numbers of patients are suffering from this disease and therefore novel medications and therapeutic approaches are urgently needed. Here, we investigated whether apelin-13, the most active member of the adipokine apelin group, could effectively suppress the development of nephropathy in Akita mouse, a spontaneous type 1 diabetic model. Apelin-13 treatment decreased diabetes-induced glomerular filtration rate, proteinuria, glomerular hypertrophy, mesangial expansion and renal inflammation. The inflammatory factors, activation of NF-κB, histone acetylation and the enzymes involved in histone acetylation were further examined in diabetic kidneys and high glucose- or sodium butyrate-treated mesangial cells in the presence or absence of apelin-13. Apelin-13 treatment inhibited diabetes-, high glucose- and NaB-induced elevation of inflammatory factors, and histone hyperacetylation by upregulation of histone deacetylase 1. Furthermore, overexpression of apelin in mesangial cells induced histone deacetylation under high glucose condition. Thus, apelin-13 may be a novel therapeutic candidate for treatment of diabetic nephropathy via regulation of histone acetylation.
AB - Diabetic nephropathy is the primary cause of end-stage renal disease. Increasing numbers of patients are suffering from this disease and therefore novel medications and therapeutic approaches are urgently needed. Here, we investigated whether apelin-13, the most active member of the adipokine apelin group, could effectively suppress the development of nephropathy in Akita mouse, a spontaneous type 1 diabetic model. Apelin-13 treatment decreased diabetes-induced glomerular filtration rate, proteinuria, glomerular hypertrophy, mesangial expansion and renal inflammation. The inflammatory factors, activation of NF-κB, histone acetylation and the enzymes involved in histone acetylation were further examined in diabetic kidneys and high glucose- or sodium butyrate-treated mesangial cells in the presence or absence of apelin-13. Apelin-13 treatment inhibited diabetes-, high glucose- and NaB-induced elevation of inflammatory factors, and histone hyperacetylation by upregulation of histone deacetylase 1. Furthermore, overexpression of apelin in mesangial cells induced histone deacetylation under high glucose condition. Thus, apelin-13 may be a novel therapeutic candidate for treatment of diabetic nephropathy via regulation of histone acetylation.
UR - http://www.scopus.com/inward/record.url?scp=84893428715&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2013.266411
DO - 10.1113/jphysiol.2013.266411
M3 - Article
C2 - 24247978
AN - SCOPUS:84893428715
VL - 592
SP - 505
EP - 521
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 3
ER -