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 treatmentEndothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C‐C Motif Chemokine Ligand 2–Mediated Angiocrine Signaling
Gao J, Wei B, Liu M, Hirsova P, Sehrawat T, Cao S, Hu X, Xue F, Yaqoob U, Kang N, Cui H, Pomerantz W, Kostallari E, Shah V. Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C‐C Motif Chemokine Ligand 2–Mediated Angiocrine Signaling. Hepatology 2021, 73: 2468-2483. PMID: 33159815, PMCID: PMC8102654, DOI: 10.1002/hep.31617.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsPartial inferior vena cava ligationPortal hypertensionLiver fibrosisLiver injuryMacrophage accumulationCCL2 transcriptionKnockout miceC motif chemokine ligand 2Inferior vena cava ligationP50 knockout miceNuclear factor kappa BVena cava ligationChemokine ligand 2Accumulation of macrophagesPathological inflammatory responsesWild-type miceFactor kappa BSinusoidal endothelial cellsInhibition of p300CCL2 deficiencyPortal pressureLiver diseaseInflammatory cellsCCL2 expression
2019
239 – Mechanotransduction-Induced Glycolysis Epigenetically Regulates a Cxcl1-Dominant Angiocrine Signaling Program in Liver Sinusoidal Endothelial Cells
Greuter T, Yaqoob U, Liu M, Huang B, Cao S, Sh V. 239 – Mechanotransduction-Induced Glycolysis Epigenetically Regulates a Cxcl1-Dominant Angiocrine Signaling Program in Liver Sinusoidal Endothelial Cells. Gastroenterology 2019, 156: s-1184. DOI: 10.1016/s0016-5085(19)39932-9.Peer-Reviewed Original ResearchMechanical 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