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- Title
Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension.
- Authors
Kumiko Muta; Yoko Obata; Satoru Oka; Shinichi Abe; Kana Minami; Mineaki Kitamura; Daisuke Endo; Takehiko Koji; Tomoya Nishino
- Abstract
Background. Although histone acetylation, an epigenetic modification, has been reported to be related to the progression of various diseases, its involvement in nephrosclerosis is unclear. Methods. Dahl salt-sensitive ratswere used as amodel of nephrosclerosis in this study. The rats were divided into three groups: (i) normal-salt diet group, (ii) high-salt diet group (HS), and (iii) HS administered daily with curcumin, a histone acetyltransferase inhibitor (HS+C). At 6 weeks after the treatment, the kidneys were dissected. Morphologic changes were assessed by Masson's trichrome staining. The number of macrophages, fibroblasts and the cells expressing acetylated histone H3 at Lys 9 (H3K9) were assessed by immunohistochemistry. Results. Although both HS and HS+C rats revealed a marked increase in systolic blood pressure, serum creatinine was increased only in HS rats at 6 weeks. In the HS rats, nephrosclerosis was induced, accompanying a significant accumulation of macrophages and fibroblasts. The inflammation and fibrosis was markedly suppressed in the HS+C group. The level of histone acetylation at Lys 9 was enhanced in the HS rats, whereas curcumin administration suppressed the histone acetylation. Moreover, in the HS rats, interleukin-6 gene expression was associated with acetylated H3K9, as revealed by chromatin immunoprecipitation assay. Conclusions. Our results suggested that curcumin ameliorates nephrosclerosis via suppression of histone acetylation, independently of hypertension.
- Subjects
NEPHROSCLEROSIS; HYPERTENSION; HISTONE acetylation; EPIGENETICS; ACETYLTRANSFERASES
- Publication
Nephrology Dialysis Transplantation, 2016, Vol 31, Issue 10, p1615
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfw036