2023
Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis
Liao C, Barrow F, Venkatesan N, Nakao Y, Mauer A, Fredrickson G, Song M, Sehrawat T, Dasgupta D, Graham R, Revelo X, Malhi H. Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis. Frontiers In Immunology 2023, 14: 1130184. PMID: 37153573, PMCID: PMC10160388, DOI: 10.3389/fimmu.2023.1130184.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsInflammationLeukocytesMaleMembrane GlycoproteinsMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseReceptors, ImmunologicSphingosine-1-Phosphate ReceptorsConceptsMurine nonalcoholic steatohepatitisNonalcoholic steatohepatitisLiver injuryHepatic macrophage accumulationT cellsIntrahepatic leukocytesDietary feedingNKT cellsMacrophage accumulationReceptor antagonismLeukocyte populationsB cellsDouble-negative T cellsReceptor-specific modulationNegative T cellsStandard chow dietImmune cell populationsC57BL/6 male miceCirculating MarkersLiver histologyProinflammatory markersNK cellsOral gavageChow dietNASH progressionLoss of CEACAM1 in endothelial cells causes hepatic fibrosis
Muturi H, Ghadieh H, Abdolahipour R, Stankus H, Belew G, Liu J, Jahromi M, Lee A, Singer B, Angeli-Pahim I, Sehrawat T, Malhi H, Verhulst S, van Grunsven L, Zarrinpar A, Duarte S, Najjar S. Loss of CEACAM1 in endothelial cells causes hepatic fibrosis. Metabolism 2023, 144: 155562. PMID: 37088122, PMCID: PMC10330196, DOI: 10.1016/j.metabol.2023.155562.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoembryonic AntigenEndothelial CellsInsulin ResistanceLiverLiver CirrhosisMaleMiceMice, Inbred C57BLNF-kappa BNon-alcoholic Fatty Liver DiseaseObesityConceptsFl/Hepatic fibrosisEndothelial lossVisceral obesityImmunohistochemical analysisWild-type HSCsEndothelial cellsHepatic fibrosis stageLiver tissue biopsiesHepatic stellate cellsNF-κB signalingLiver endothelial cellsNF-κB targetsLiver transplantAdult patientsBariatric surgerySystemic inflammationInflammatory infiltrationLiver biopsyNASH pathogenesisInsulin resistanceFibrosis stageInsulin sensitivityHepatic fibrogenesisMale mice
2021
Circulating extracellular vesicles are a biomarker for NAFLD resolution and response to weight loss surgery
Nakao Y, Amrollahi P, Parthasarathy G, Mauer A, Sehrawat T, Vanderboom P, Nair K, Nakao K, Allen A, Hu T, Malhi H. Circulating extracellular vesicles are a biomarker for NAFLD resolution and response to weight loss surgery. Nanomedicine Nanotechnology Biology And Medicine 2021, 36: 102430. PMID: 34174416, PMCID: PMC8418232, DOI: 10.1016/j.nano.2021.102430.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkersExtracellular VesiclesFemaleHepatocytesHumansMaleMiddle AgedNon-alcoholic Fatty Liver DiseaseWeight LossConceptsWeight loss surgeryHepatocyte-derived extracellular vesiclesPlasma levelsNAFLD resolutionExtracellular vesiclesWeight loss patientsLogistic regression analysisPlasma extracellular vesiclesNAFLD patientsLipid panelNASH patientsLoss patientsNAFLDInvasive biomarkersPatientsCare testGroup 22EV correlatesSteatosisSurgeryRegression analysisBiomarkersDifferential ultracentrifugationCorrelatesInflammation
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 ResearchMeSH KeywordsAnimalsCeramidesDisease Models, AnimalEndoribonucleasesExtracellular VesiclesHepatocytesMaleMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseProtein Serine-Threonine KinasesConceptsX-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