FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4224744484> ?p ?o ?g. }

• W4224744484 endingPage "2057" @default.
• W4224744484 startingPage "2042" @default.
• W4224744484 abstract "Abstract Alcohol-associated liver disease is a major cause of alcohol-related mortality. However, the mechanisms underlying disease progression are not fully understood. Recently we found that liver molecular pathways are altered by alcohol consumption differently in males and females. We were able to associate these sex-specific pathways with two upstream regulators: H3K4-specific demethylase enzymes KDM5B and KDM5C. Mice were fed the Lieber-DeCarli alcohol liquid diet for 3 weeks or a combination of a high-fat diet with alcohol in water for 16 weeks (western diet alcohol model [WDA] model). To assess the role of histone demethylases, mice were treated with AAV-shControl, AAV-shKdm5b, and/or AAV-shKdm5c and/or AAV-shAhR vectors. Gene expression and epigenetic changes after Kdm5b/5c knockdown were assessed by RNA-sequencing and H3K4me3 chromatin immunoprecipitation analysis. We found that less than 5% of genes affected by Kdm5b / Kdm5c knockdown were common between males and females. In females, Kdm5b / Kdm5c knockdown prevented fibrosis development in mice fed the WDA alcohol diet for 16 weeks and decreased fibrosis-associated gene expression in mice fed the Lieber-DeCarli alcohol liquid diet. In contrast, fibrosis was not affected by Kdm5b / Kdm5c knockdown in males. We found that KDM5B and KDM5C promote fibrosis in females through down-regulation of the aryl hydrocarbon receptor (AhR) pathway components in hepatic stellate cells. Kdm5b / Kdm5c knockdown resulted in an up-regulation of Ahr, Arnt , and Aip in female but not in male mice, thus preventing fibrosis development. Ahr knockdown in combination with Kdm5b/Kdm5c knockdown restored profibrotic gene expression. Conclusion: KDM5 demethylases contribute to differences between males and females in the alcohol response in the liver. The KDM5/AhR axis is a female-specific mechanism of fibrosis development in alcohol-fed mice. In this study we report that in female mice, alcohol induces KDM5B and KDM5C in hepatic stellate cells to promote AhR downregulation and fibrosis development; liver knockdown of Kdm5b and Kdm5c can prevent AhR downregulation and fibrosis development in females but not in males. Relationship between KDM5 demethylases and fibrosis is female specific in humans as well. Potentially our study is the first step to future sex-specific therapy for Alcohol-associated Liver Disease." @default.
• W4224744484 created "2022-04-27" @default.
• W4224744484 creator A5029700070 @default.
• W4224744484 creator A5041609454 @default.
• W4224744484 creator A5057107186 @default.
• W4224744484 creator A5070269081 @default.
• W4224744484 creator A5074531733 @default.
• W4224744484 date "2022-08-01" @default.
• W4224744484 modified "2023-10-12" @default.
• W4224744484 title "Alcohol-associated fibrosis in females is mediated by female-specific activation of lysine demethylases KDM5B and KDM5C" @default.
• W4224744484 cites W1511559120 @default.
• W4224744484 cites W1981177186 @default.
• W4224744484 cites W2002070115 @default.
• W4224744484 cites W2014049736 @default.
• W4224744484 cites W2017557941 @default.
• W4224744484 cites W2024052509 @default.
• W4224744484 cites W2045974460 @default.
• W4224744484 cites W2054659582 @default.
• W4224744484 cites W2055452745 @default.
• W4224744484 cites W2056163657 @default.
• W4224744484 cites W2069089843 @default.
• W4224744484 cites W2112131993 @default.
• W4224744484 cites W2123535222 @default.
• W4224744484 cites W2129234412 @default.
• W4224744484 cites W2150782426 @default.
• W4224744484 cites W2153256126 @default.
• W4224744484 cites W2156596890 @default.
• W4224744484 cites W2218756884 @default.
• W4224744484 cites W2235911259 @default.
• W4224744484 cites W2265965695 @default.
• W4224744484 cites W2274242949 @default.
• W4224744484 cites W2294848537 @default.
• W4224744484 cites W2401470494 @default.
• W4224744484 cites W2559913705 @default.
• W4224744484 cites W2598621195 @default.
• W4224744484 cites W2610185685 @default.
• W4224744484 cites W2755856543 @default.
• W4224744484 cites W2762689365 @default.
• W4224744484 cites W2802744456 @default.
• W4224744484 cites W2803237326 @default.
• W4224744484 cites W2806330652 @default.
• W4224744484 cites W2883853179 @default.
• W4224744484 cites W2884304683 @default.
• W4224744484 cites W2897917666 @default.
• W4224744484 cites W2906786937 @default.
• W4224744484 cites W2924425749 @default.
• W4224744484 cites W2948955892 @default.
• W4224744484 cites W2985431905 @default.
• W4224744484 cites W2986132968 @default.
• W4224744484 cites W2990388687 @default.
• W4224744484 cites W3005481769 @default.
• W4224744484 cites W3027202411 @default.
• W4224744484 cites W3041091510 @default.
• W4224744484 cites W3080101183 @default.
• W4224744484 cites W3100602732 @default.
• W4224744484 cites W3134285382 @default.
• W4224744484 cites W3164270558 @default.
• W4224744484 cites W3176328584 @default.
• W4224744484 cites W3201387363 @default.
• W4224744484 cites W4210804107 @default.
• W4224744484 doi "https://doi.org/10.1002/hep4.1967" @default.
• W4224744484 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35468265" @default.
• W4224744484 hasPublicationYear "2022" @default.
• W4224744484 type Work @default.
• W4224744484 citedByCount "6" @default.
• W4224744484 countsByYear W42247444842022 @default.
• W4224744484 countsByYear W42247444842023 @default.
• W4224744484 crossrefType "journal-article" @default.
• W4224744484 hasAuthorship W4224744484A5029700070 @default.
• W4224744484 hasAuthorship W4224744484A5041609454 @default.
• W4224744484 hasAuthorship W4224744484A5057107186 @default.
• W4224744484 hasAuthorship W4224744484A5070269081 @default.
• W4224744484 hasAuthorship W4224744484A5074531733 @default.
• W4224744484 hasBestOaLocation W42247444841 @default.
• W4224744484 hasConcept C104317684 @default.
• W4224744484 hasConcept C126322002 @default.
• W4224744484 hasConcept C173396325 @default.
• W4224744484 hasConcept C2781364455 @default.
• W4224744484 hasConcept C41091548 @default.
• W4224744484 hasConcept C54355233 @default.
• W4224744484 hasConcept C71924100 @default.
• W4224744484 hasConcept C86803240 @default.
• W4224744484 hasConceptScore W4224744484C104317684 @default.
• W4224744484 hasConceptScore W4224744484C126322002 @default.
• W4224744484 hasConceptScore W4224744484C173396325 @default.
• W4224744484 hasConceptScore W4224744484C2781364455 @default.
• W4224744484 hasConceptScore W4224744484C41091548 @default.
• W4224744484 hasConceptScore W4224744484C54355233 @default.
• W4224744484 hasConceptScore W4224744484C71924100 @default.
• W4224744484 hasConceptScore W4224744484C86803240 @default.
• W4224744484 hasIssue "8" @default.
• W4224744484 hasLocation W42247444841 @default.
• W4224744484 hasLocation W42247444842 @default.
• W4224744484 hasLocation W42247444843 @default.
• W4224744484 hasOpenAccess W4224744484 @default.
• W4224744484 hasPrimaryLocation W42247444841 @default.
• W4224744484 hasRelatedWork W2002128513 @default.
• W4224744484 hasRelatedWork W2076883844 @default.

• next