Featured Publications
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 injectionQuantitative assessment of portal hypertension with bi-parametric dual-frequency hepatic MR elastography in mouse models
Li J, Sehrawat T, Chen J, Hilscher M, Glaser K, Arab J, De Assuncao T, Simonetto D, Mounajjed T, Manduca A, Ehman R, Shah V, Yin M. Quantitative assessment of portal hypertension with bi-parametric dual-frequency hepatic MR elastography in mouse models. European Radiology 2020, 31: 2303-2311. PMID: 33026502, PMCID: PMC7981248, DOI: 10.1007/s00330-020-07341-3.Peer-Reviewed Original ResearchConceptsPortal hypertensionPortal pressureHepatic MR elastographyMouse modelHigh diagnostic accuracyDiagnostic accuracyHepatic fibrosisMR elastographyWild-type male miceHypertension mouse modelSignificant portal hypertensionCholestatic liver injuryCholestatic liver diseaseLiver MR elastographySham miceLiver diseaseLiver injuryHepatic congestionLiver fibrosisMale micePreclinical modelsTreatment efficacyFibrosisHypertensionDeLong test
2024
Liver Sinusoidal Endothelial Cells Contribute to Portal Hypertension Through Collagen Type IV–Driven Sinusoidal Remodeling
Gan C, Yaqoob U, Lu J, Xie M, Anwar A, Jalan-Sakrikar N, Jerez S, Sehrawat T, Navarro-Corcuera A, Kostallari E, Habash N, Cao S, Shah V. Liver Sinusoidal Endothelial Cells Contribute to Portal Hypertension Through Collagen Type IV–Driven Sinusoidal Remodeling. JCI Insight 2024, 9: e174775. PMID: 38713515, PMCID: PMC11382879, DOI: 10.1172/jci.insight.174775.Peer-Reviewed Original ResearchLiver sinusoidal endothelial cellsPortal hypertensionSinusoidal remodelingSinusoidal endothelial cellsSinusoidal resistanceComplication of liver cirrhosisEndothelial cellsSinusoidal endothelial cells in vitroEnhancer-promoter interactionsEpigenome editing approachesEndothelial cells in vitroChronic liver injuryCells in vitroMouse fibrotic liversCollagen type IVLiver cirrhosisGene mutationsExpression regulationLiver fibrosisLiver injuryEpigenetic repressionLiver diseaseCellular sourceCol4 expressionImmunofluorescence staining
2021
Endothelial 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
2020
GIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway
Yaqoob U, Luo F, Greuter T, Sakrikar N, Sehrawat T, Lu J, Hu X, Gao J, Kostallari E, Chen J, Arab J, Martin-Mateos R, Cao S, Shah V. GIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway. Cellular And Molecular Gastroenterology And Hepatology 2020, 10: 545-559. PMID: 32447051, PMCID: PMC7399184, DOI: 10.1016/j.jcmgh.2020.05.005.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAdaptor Proteins, Signal TransducingAnimalsBiomarkersCell MovementCells, CulturedDisease Models, AnimalEpigenesis, GeneticGene Knockdown TechniquesHepatic Stellate CellsHistonesHumansHypertension, PortalInsulin-Like Growth Factor Binding Protein 3Integrin beta1Liver CirrhosisMiceMice, KnockoutPhosphorylationPrimary Cell CultureSignal TransductionTransforming Growth Factor betaUp-RegulationConceptsHepatic stellate cellsPortal hypertensionIGFBP-3Quantitative polymerase chain reactionWestern blot analysisLiver fibrosisPolymerase chain reactionHSC migrationChromatin immunoprecipitationChronic liver injury modelInsulin-like growth factorActivation targetGrowth factorQuiescent hepatic stellate cellsIGFBP-3 increaseTransport proteinsChronic liver diseaseChain reactionLiver injury modelIntegrin-dependent phosphorylationHistone 3 lysine 27 acetylationGene regulation changesHSC activation markersEnzyme-linked immunosorbent assayEnzyme-linked immunosorbent