2021
Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis
Liu M, Cao S, He L, Gao J, Arab J, Cui H, Xuan W, Gao Y, Sehrawat T, Hamdan F, Ventura-Cots M, Argemi J, Pomerantz W, Johnsen S, Lee J, Gao F, Ordog T, Mathurin P, Revzin A, Bataller R, Yan H, Shah V. Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis. Nature Communications 2021, 12: 4560. PMID: 34315876, PMCID: PMC8316465, DOI: 10.1038/s41467-021-24843-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokinesCytokinesDisease Models, AnimalEndothelial CellsEnhancer Elements, GeneticEpigenesis, GeneticGene Expression RegulationHepatitis, AlcoholicHistonesHumansLipopolysaccharidesLiverMice, Inbred C57BLNeutrophilsNF-kappa BPromoter Regions, GeneticRNA-SeqSignal TransductionTranscription FactorsTumor Necrosis Factor-alphaConceptsAlcoholic hepatitisLiver sinusoidal endothelial cellsChemokine expressionNeutrophil infiltrationLiver neutrophil infiltrationTNFα/NF-κB signalingNF-κB signalingHuman liver explantsElevated chemokine expressionSinusoidal endothelial cellsCXCL expressionChemokine productionCXCL chemokinesCytokine pathwaysCytokines TNFαInflammatory signalingMurine modelLiver explantsTherapeutic potentialPharmacologic inhibitionExtraterminal (BET) proteinsBET inhibitionHuman liverEndothelial cellsAH treatment
2020
IRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis
Dasgupta D, Nakao Y, Mauer A, Thompson J, Sehrawat T, Liao C, Krishnan A, Lucien F, Guo Q, Liu M, Xue F, Fukushima M, Katsumi T, Bansal A, Pandey M, Maiers J, DeGrado T, Ibrahim S, Revzin A, Pavelko K, Barry M, Kaufman R, Malhi H. IRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis. Gastroenterology 2020, 159: 1487-1503.e17. PMID: 32574624, PMCID: PMC7666601, DOI: 10.1053/j.gastro.2020.06.031.Peer-Reviewed Original ResearchConceptsX-box binding protein 1Release of EVsHepatocyte-derived extracellular vesiclesSerine palmitoyltransferase genesExtracellular vesiclesSerine palmitoyltransferaseChromatin immunoprecipitationCeramide biosynthesisInflammatory Extracellular VesiclesMonocyte-derived macrophagesUnfolded protein responseNonalcoholic steatohepatitisDiet-induced steatohepatitisGene expression analysisPrimary hepatocytesNumber of EVsBinding protein 1Cultured primary hepatocytesNanoparticle-tracking analysisNanoscale flow cytometryIRE1ALiver tissueRate-limiting enzymeProtein responseExpression analysis
2019
Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension
Hilscher M, Sehrawat T, Arab J, Zeng Z, Gao J, Liu M, Kostallari E, Gao Y, Simonetto D, Yaqoob U, Cao S, Revzin A, Beyder A, Wang R, Kamath P, Kubes P, Shah V. Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension. Gastroenterology 2019, 157: 193-209.e9. PMID: 30872106, PMCID: PMC6581607, DOI: 10.1053/j.gastro.2019.03.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium SignalingCapillariesChemokine CXCL1Endothelial CellsExtracellular TrapsHydrolasesHypertension, PortalIn Vitro TechniquesIntegrinsLeukocyte ElastaseLigationLiverMechanotransduction, CellularMiceMice, Inbred C57BLMice, KnockoutNeutrophil InfiltrationPortal PressureProtein-Arginine Deiminase Type 4Receptor, Notch1Stress, MechanicalThrombosisVena Cava, InferiorConceptsLiver sinusoidal endothelial cellsPortal hypertensionBile duct ligationPortal pressureSinusoidal endothelial cellsFormation of NETsPrimary liver sinusoidal endothelial cellsMechanical stretchControl micePeptidyl arginine deiminase type IVTreatment of PHUnderwent bile duct ligationSuprahepatic inferior vena cavaEndothelial cellsLower portal pressureNeutrophil chemoattractant CXCL1Intravital imagingExpression of CXCL1Inferior vena cavaRecruit neutrophilsNeutrophil recruitmentC57BL/6 miceVena cavaLess fibrinSubcutaneous injection