title: Apelin inhibits the development of diabetic nephropathy by regulating histone acetylation in Akita mouse.
abstract: 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.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China.  lzheng217@hotmail.com; Kun Huang: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.   Email: kunhuang2008@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Jianshuang
authors.initials: J
authors.lastname: Li
authors.forename: Lihua
authors.initials: L
authors.lastname: Jiao
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.forename: Anlin
authors.initials: A
authors.lastname: Peng
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
mesh_terms: D000107:Acetylation; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006657:Histones / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*
chemical_list: D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; C495199:apelin-13 peptide