Klotho recovery by genistein via promoter histone acetylation and DNA demethylation mitigates renal fibrosis in mice

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Yanning LiWangsen Cao

Abstract

Renal fibrosis is a common histomorphological feature of renal aging and chronic kidney diseases of all etiologies, and its initiation and progression are substantially influenced by aberrant epigenetic modifications of fibrosis-susceptible genes, yet without effective therapy. "Epigenetic diets" exhibit tissue-protective and epigenetic-modulating properties; however, their anti-renal fibrosis functions and the underlying mechanisms are less understood. In this study, we show that genistein, a phytoestrogenic isoflavone enriched in dietary soy products, exhibits impressive anti-renal fibrosis activities by recovering epigenetic loss of Klotho, a kidney-enriched anti-aging and fibrosis-suppressing protein. Mouse fibrotic kidneys induced by UUO (unilateral ureteral occlusion) displayed severer Klotho suppression and adverse expression of renal fibrosis-associated proteins, but genistein administration markedly recovered the Klotho loss and attenuated renal fibrosis and the protein expression abnormalities. The examination of possible causes of the Klotho recovery revealed that genistein simultaneously inhibited histone 3 deacetylation of Klotho promoter and normalized the promoter DNA hypermethylation by suppressing elevated DNA ...Continue Reading

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Citations

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Methods Mentioned

BETA
histone acetylation
acetylation
transgenic
immunoprecipitation
PCR
electrophoresis
ChIP

Software Mentioned

Image J
MethPrimer

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