BACKGROUND _ AIMS: @entity285 is a primary cause of @entity409 and an important co-morbidity factor in other causes of @entity409 . A common feature of progressive @entity409 is @entity82 , which results from the net deposition of fibril-forming extracellular matrix (ECM). The hepatic stellate cell (HSC) is widely considered to be the major cellular source of fibrotic ECM. We determined if HSCs are responsive to direct stimulation by @entity285 . METHODS: HSCs undergoing transdifferentiation were incubated with @entity1068 and expression of fibrogenic genes and epigenetic regulators was measured. Mechanisms responsible for recorded changes were investigated using ChIP-Seq and bioinformatics analysis. @entity1068 induced changes were confirmed using HSCs isolated from a @entity19 @entity285 model and from @entity8019 @entity1 's liver and through precision cut liver slices. RESULTS: HSCs responded to @entity1068 exposure by increasing profibrogenic and ECM gene expression including @entity2362 . @entity1068 induced an altered expression of multiple epigenetic regulators, indicative of a potential to modulate chromatin structure during HSC transdifferentiation. @entity11626 , a histone 3 @entity376 4 (H3K4) methyltransferase, was induced by @entity1068 and recruited to the @entity2362 gene promoter where it was associated with enriched H3K4me3, a mark of active chromatin. Chromatin immunoprecipitation sequencing (ChIPseq) revealed that @entity1068 has broad effects on the HSC epigenome and identified 41 gene loci at which both MML1 and its H3K4me3 mark were enriched in response to @entity1068 . CONCLUSIONS: @entity1068 directly influences HSC transdifferentiation by stimulating global changes in chromatin structure, resulting in the increased expression of ECM proteins. The ability of @entity285 to remodel the epigenome during HSC transdifferentiation provides mechanisms for it to act as a co-morbidity factor in @entity409 .

XXXX directly stimulates epigenetic modifications in hepatic stellate cells.

@entity1 :: ('9606', 'Species') :: ['patient'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity2362 :: ('2006', 'Gene') :: ['elastin'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity11626 :: ('4297', 'Gene') :: ['MLL1'] @entity409 :: ('MESH:D008107', 'Disease') :: ['liver disease'] @entity8019 :: ('MESH:D000326', 'Disease') :: ['ALD'] @entity376 :: ('CHEBI:25094', 'Chemical') :: ['lysine'] @entity285 :: ('D000431', 'Chemical') :: ['alcohol', 'Alcohol'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['Ethanol', 'ethanol']
@entity285 :: (D000431,Chemical) :: ['Alcohol']
