期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 41, 期 1, 页码 95-106出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2017.3218
关键词
histone deacetylase inhibitor; fibroblast; inflammation; kidney fibrosis; extracellular matrix
资金
- National Research Foundation of Korea (NRF) - Korean government [NRF-2015R1D1A3A03015653, NRF-2014R1A1A4A01003832]
- Chonbuk National University
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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