2022
Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo
Greuter T, Yaqoob U, Gan C, Jalan-Sakrikar N, Kostallari E, Lu J, Gao J, Sun L, Liu M, Sehrawat TS, Ibrahim SH, Furuta K, Nozickova K, Huang BQ, Gao B, Simons M, Cao S, Shah VH. Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo. Journal Of Hepatology 2022, 77: 723-734. PMID: 35421427, PMCID: PMC9391258, DOI: 10.1016/j.jhep.2022.03.029.Peer-Reviewed Original ResearchConceptsFocal adhesionsGlycolytic enzymesIsolated focal adhesionsChromosome conformation captureHistone activation marksChromatin immunoprecipitation analysisConformation captureChIP sequencingActivation marksEpigenetic regulationActin dynamicsHistone acetylationRNA sequencingERT2 miceActin polymerizationEndothelial cellsCXCL1 promoterNovel roleIntegrin β1Druggable targetsInhibition of glycolysisNuclear chromatinGlycolysisAngiocrineEnzyme
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 treatmentCirculating Extracellular Vesicles Carrying Sphingolipid Cargo for the Diagnosis and Dynamic Risk Profiling of Alcoholic Hepatitis
Sehrawat T, Arab J, Liu M, Amrollahi P, Wan M, Fan J, Nakao Y, Pose E, Navarro‐Corcuera A, Dasgupta D, Liao C, He L, Mauer A, Avitabile E, Ventura‐Cots M, Bataller R, Sanyal A, Chalasani N, Heimbach J, Watt K, Gores G, Gines P, Kamath P, Simonetto D, Hu T, Shah V, Malhi H. Circulating Extracellular Vesicles Carrying Sphingolipid Cargo for the Diagnosis and Dynamic Risk Profiling of Alcoholic Hepatitis. Hepatology 2021, 73: 571-585. PMID: 32246544, PMCID: PMC7541595, DOI: 10.1002/hep.31256.Peer-Reviewed Original ResearchConceptsEnd-stage liver diseaseAlcohol-associated cirrhosisAlcoholic hepatitisAH subjectsHealthy controlsHeavy drinkersLiver diseaseEtiology of ESLDEV concentrationEnd-stage liver disease (MELD) scoreExtracellular vesiclesRisk profilingPathogenesis of AHLiver Disease scoreCholestatic liver diseaseNonalcoholic steatohepatitisRisk stratificationClinical criteriaPrognostic performanceDisease scoreDiagnostic biomarkersDisease controlEV countsDiseaseDrinkers
2019
Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs
Shaheen M, Joo D, Ross J, Anderson B, Chen H, Huebert R, Li Y, Amiot B, Young A, Zlochiver V, Nelson E, Mounajjed T, Dietz A, Michalak G, Steiner B, Davidow D, Paradise C, van Wijnen A, Shah V, Liu M, Nyberg S. Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. Nature Biomedical Engineering 2019, 4: 437-445. PMID: 31611679, PMCID: PMC7153989, DOI: 10.1038/s41551-019-0460-x.Peer-Reviewed Original ResearchConceptsHuman endothelial cellsEndothelial cellsSustained perfusionImmune responseContinuous perfusionNormal liver tissueHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsImmunosuppression protocolsAnticoagulation therapyVein endothelial cellsImmunosuppressed pigsEndothelial markersLiver sinusoidsPerfusionLiver tissueHuman liverLiverBlood perfusionHeterotopic implantationMain predictorsLiver scaffoldsPigsPorcine liverDaysMechanical 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