Valproate attenuates diabetic nephropathy through inhibition of endoplasmic reticulum stress‑induced apoptosis

Sun,Xin‑Yi; Qin,Han‑Jiao; Zhang,Ze; Xu,Ye; Yang,Xiao‑Chun; Zhao,Dong‑Ming; Li,Xiao‑Ning; Sun,Lian‑Kun

doi:10.3892/mmr.2015.4580

Valproate attenuates diabetic nephropathy through inhibition of endoplasmic reticulum stress‑induced apoptosis

Authors:
- Xin‑Yi Sun
- Han‑Jiao Qin
- Ze Zhang
- Ye Xu
- Xiao‑Chun Yang
- Dong‑Ming Zhao
- Xiao‑Ning Li
- Lian‑Kun Sun
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Affiliations: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Endocrinology and Metabolism, First Clinical Hospital of Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Clinical Medicine, Norman Bethune Health Science Center, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Histology and Embryology, Medical Research Laboratory, Jilin Medical College, Changchun, Jilin 132013, P.R. China, Department of Endocrinology and Metabolism, Affiliated Hospital of Beihua University, Changchun, Jilin 132011, P.R. China
Published online on: November 19, 2015 https://doi.org/10.3892/mmr.2015.4580
Pages: 661-668
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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