title: Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension.
abstract: Although histone acetylation, an epigenetic modification, has been reported to be related to the progression of various diseases, its involvement in nephrosclerosis is unclear.
  
  
  
  Dahl salt-sensitive rats were used as a model 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.
  
  
  
  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.
  
  
  
  Our results suggested that curcumin ameliorates nephrosclerosis via suppression of histone acetylation, independently of hypertension.
authors.affiliation: Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan Center for Comprehensive Community Care Education, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Muta
authors.affiliation: Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan Medical Education Development Center, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Obata
authors.affiliation: Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Oka
authors.affiliation: Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Minami
authors.affiliation: Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Mineaki
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Endo
authors.affiliation: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.affiliation: Department of Nephrology, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nishino
mesh_terms: D000107:Acetylation; D000818:Animals; D001794:Blood Pressure; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D044127:Epigenesis, Genetic / Q000187:drug effects; D015870:Gene Expression; D006657:Histones / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009400:Nephrosclerosis / Q000188:drug therapy* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D020303:Rats, Inbred Dahl
chemical_list: D006657:Histones; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D003474:Curcumin
keywords: CKD; chronic inflammation; glomerulosclerosis; hypertension; interleukin-6