title: Valproate attenuates diabetic nephropathy through inhibition of endoplasmic reticulum stress‑induced apoptosis.
abstract: Previous studies have suggested that endoplasmic reticulum stress (ERS) is one of the mechanisms responsible for the pathogenesis of diabetic nephropathy (DN). Histone acetylation modification can regulate the transcription of genes and is involved in the regulation of ERS. Valproate (VPA), a nonselective histone deacetylase inhibitor, has been reported to have a protective role in kidney tissue injury, however, whether VPA can prevent DN remains to be elucidated. In the present study, it was found that VPA increases the expression of glucose‑regulated protein (GRP78) and reduces the protein expression of C/EBP‑homologous protein (CHOP), growth arrest and DNA‑damage‑inducible gene 153 and caspase‑12 in a rat model of DN. VPA can reduce renal cell apoptosis and alleviate proteinuria and alterations in serum creatinine. VPA also upregulates the acetylation level of histone H4 in the promoter of GRP78 and downregulates the acetylation level of histone H4 in the promoter of CHOP. Collectively, the data indicate that VPA can relieve ERS and reduce renal cell apoptosis, and thus attenuate renal injury in a rat model of DN by regulating the acetylation level of histone H4 in ERS‑associated protein promoters.
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Sun
authors.affiliation: Department of Endocrinology and Metabolism, First Clinical Hospital of Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Han-Jiao
authors.initials: HJ
authors.lastname: Qin
authors.affiliation: Department of Clinical Medicine, Norman Bethune Health Science Center, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Medical Research Laboratory, Jilin Medical College, Changchun, Jilin 132013, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Yang
authors.affiliation: Department of Endocrinology and Metabolism, Affiliated Hospital of Beihua University, Changchun, Jilin 132011, P.R. China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Lian-Kun
authors.initials: LK
authors.lastname: Sun
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics; D006657:Histones / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017208:Rats, Wistar; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006657:Histones; D051742:Transcription Factor CHOP; D014635:Valproic Acid