Epigenetic Histone Modifications Involved in Profibrotic Gene Regulation by XXXX and Its Oxidized Lipid Products in @entity2316 .

@entity8 @entity82 @entity20180 @entity6 @entity2316 @entity2299 @entity641 @entity19 @entity11903 @entity376 @entity71715
AIMS: Epigenetic mechanisms, including histone post-translational modifications and DNA methylation, are implicated in the pathogenesis of @entity2316 ( @entity2316 ), but the mediators are not well known. Moreover, although @entity2299 contributes to @entity2316 , epigenetic changes triggered by lipids are unclear. In @entity6 , increased expression of @entity20180 (12/15-LO) enhances oxidized lipids such as @entity11903 [ @entity11903 ], which promote oxidant stress, @entity8 , and @entity82 , and mediate the actions of profibrotic growth factors. We hypothesized that 12/15-LO and its oxidized lipid products can regulate epigenetic mechanisms mediating profibrotic gene expression related to @entity2316 . RESULTS: @entity11903 increased profibrotic gene expression and enrichment of permissive histone @entity376 modifications at their promoters in MCs. @entity11903 also increased protein levels of @entity71715 , a histone H3 @entity376 4 methyltransferase, and promoted its nuclear translocation and enrichment at profibrotic gene promoters. Furthermore, @entity71715 ( @entity71715 ) gene silencing inhibited @entity11903 -induced profibrotic gene expression. 12/15-LO ( @entity20180 ) gene silencing or genetic knockout inhibited @entity641 ( @entity641 )-induced expression of @entity71715 and profibrotic genes and histone modifications in MCs. Furthermore, 12/15-LO knockout in @entity19 ameliorated key features of @entity2316 and abrogated increases in renal @entity71715 and profibrotic genes. Additionally, 12/15-LO siRNAs in vivo blocked increases in renal @entity71715 and profibrotic genes in @entity6 @entity19 . Innovation and Conclusion: These novel results demonstrate for the first time that 12/15-LO-derived oxidized lipids regulate histone modifications associated with profibrotic gene expression in MCs, and 12/15-LO can mediate similar actions of @entity641 and @entity6 . Targeting 12/15-LO might be a useful strategy to inhibit key epigenetic mechanisms involved in @entity2316 . Antioxid. Redox Signal. 00, 000-000.
