Inhibition of histone deacetylase 1 ameliorates renal tubulointerstitial fibrosis via modulation of inflammation and extracellular matrix gene transcription in mice

Nguyễn-Thanh,Tùng; Kim,Dal; Lee,Sik; Kim,Won; Park,Sung Kwang; Kang,Kyung Pyo

doi:10.3892/ijmm.2017.3218

Inhibition of histone deacetylase 1 ameliorates renal tubulointerstitial fibrosis via modulation of inflammation and extracellular matrix gene transcription in mice

Authors:
- Tùng Nguyễn-Thanh
- Dal Kim
- Sik Lee
- Won Kim
- Sung Kwang Park
- Kyung Pyo Kang
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Affiliations: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Jeollabuk 54907, Republic of Korea
Published online on: October 27, 2017 https://doi.org/10.3892/ijmm.2017.3218
Pages: 95-106
Copyright: © Nguyễn-Thanh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Renal tubulointerstitial fibrosis is characterized by sustained inflammation and excessive extracellular matrix (ECM) accumulation, leading to chronic kidney disease. Valproic acid (VPA) has anticancer activity through regulation of cell differentiation and apoptosis via inhibition of histone deacetylase (HDAC) activity and is considered a class I HDAC inhibitor. In this study, the effect of VPA on unilateral ureteral obstruction (UUO)‑induced renal fibrosis by modulation of renal inflammation and ECM gene transcription was investigated. VPA treatment increased histone H3 acetylation in both sham‑ and UUO‑operated kidneys and decreased the UUO‑induced increase in tubular injury and ECM deposition in mice. VPA also decreased myofibroblast activation and proliferation in UUO kidneys and NRK‑49F cells. Finally, it was demonstrated that the anti‑fibrotic effect of VPA was associated with regulation of ECM protein promoter enrichment at an acetylated histone H3 site. In conclusion, the findings indicate that VPA may have a beneficial effect on UUO‑induced renal fibrosis via regulation of myofibroblast activation, proliferation, and ECM protein production by chromatin remodeling and ECM protein promoter transcription.

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