Key messages
Genistein prevents renal fibrosis and the associated Klotho suppression in UUO mice. Genistein upregulates Klotho in part by reversing the promoter histone 3 hypoacetylation. Genistein also preserves Klotho via relieving Klotho promoter hypermethylation. Genistein demethylates Klotho promoter by inhibiting aberrant DNMT1/3a expression. Genistein restoration of Klotho is essential for its anti-renal fibrosis function.