The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in XXXX .

@entity644 @entity6 @entity26660 @entity2316 @entity26 @entity22228 @entity71059 @entity376 @entity35 @entity413
UNASSIGNED: Epigenetic regulation of oxidative stress is emerging as a critical mediator of @entity2316 . In @entity6 , oxidative damage occurs when there is an imbalance between reactive @entity26 species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 ( @entity71059 ) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor @entity22228 ( @entity22228 ). Pharmacologic or genetic depletion of @entity71059 augmented @entity22228 expression and oxidative stress in podocytes cultured under high- @entity413 conditions. Conversely, @entity71059 upregulation through inhibition of its regulatory microRNA, microRNA-101, downregulated @entity22228 and attenuated oxidative stress. In @entity6 @entity35 , depletion of @entity71059 decreased histone 3 @entity376 27 trimethylation (H3K27me3), increased glomerular @entity22228 expression, induced podocyte injury, and augmented oxidative stress and @entity644 . Chromatin immunoprecipitation sequencing revealed H3K27me3 enrichment at the promoter of the transcription factor @entity26660 , which was upregulated on @entity71059 depletion and bound to the @entity22228 promoter, controlling expression of its gene product. In high @entity413 -exposed podocytes and the kidneys of @entity6 @entity35 , the lower @entity71059 expression detected coincided with upregulation of @entity26660 and @entity22228 . Finally, in a gene expression array, @entity22228 was among seven of 30,854 genes upregulated by high @entity413 , @entity71059 depletion, and the combination thereof. Thus, @entity71059 represses the transcription factor @entity26660 , which controls expression of the antioxidant inhibitor @entity22228 , and in @entity6 , downregulation of @entity71059 promotes oxidative stress. These findings expand the extent to which epigenetic processes affect the @entity6 kidney to include antioxidant repair.
