Featured Publications
Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, Pongratz RL, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metabolism 2018, 27: 339-350.e3. PMID: 29414684, PMCID: PMC5806149, DOI: 10.1016/j.cmet.2018.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell NucleusChromatinDigoxinDisease Models, AnimalEndotoxinsHistonesHumansHypoxia-Inducible Factor 1, alpha SubunitInflammationLiverNon-alcoholic Fatty Liver DiseaseOxidation-ReductionProtein BindingPyruvate KinaseTHP-1 CellsTranscription, GeneticTranscriptional ActivationConceptsHIF-1α transactivationSterile inflammationHIF-1α pathway activationNon-alcoholic steatohepatitisKinase M2Major clinical consequencesAbility of digoxinLiver inflammationLiver diseasePyruvate kinase M2Clinical consequencesTherapeutic targetInflammationTissue damageHIF-1αPathway activationDigoxinOxidative stressCardiac glycosidesSteatohepatitisDigoxin bindsNovel roleLiverUbiquitous responseActivation
2020
Glycogen synthase kinase-3β inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarction
Wang S, Su X, Xu L, Chang C, Yao Y, Komal S, Cha X, Zang M, Ouyang X, Zhang L, Han S. Glycogen synthase kinase-3β inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarction. Journal Of Molecular And Cellular Cardiology 2020, 149: 82-94. PMID: 32991876, DOI: 10.1016/j.yjmcc.2020.09.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCARD Signaling Adaptor ProteinsEnzyme ActivationFibroblastsGlycogen Synthase Kinase 3 betaIndolesInflammasomesInflammationMaleMaleimidesMyocardial InfarctionMyocardial IschemiaMyocytes, CardiacNLR Family, Pyrin Domain-Containing 3 ProteinProtein Kinase InhibitorsProtein MultimerizationRats, Sprague-DawleyVascular RemodelingConceptsNLRP3 inflammasome activationGSK-3β inhibitionMyocardial infarctionInflammasome activationNOD-like receptor family pyrin domainGSK-3βFamily pyrin domainGlycogen synthase kinase-3β inhibitionCardiac dysfunctionMyocardial dysfunctionCardiac damageHeart dysfunctionHeart diseaseSterile inflammationInflammatory responseRat modelDay 2Pyrin domainCardiac fibroblastsSuccessful inductionHypoxia treatmentDysfunctionGSK-3 activityHuman cardiomyocytesInflammasome stimulation
2018
β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway
Chen Y, Ouyang X, Hoque R, Garcia-Martinez I, Yousaf MN, Tonack S, Offermanns S, Dubuquoy L, Louvet A, Mathurin P, Massey V, Schnabl B, Bataller R, Mehal WZ. β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. Journal Of Hepatology 2018, 69: 687-696. PMID: 29705237, PMCID: PMC6098974, DOI: 10.1016/j.jhep.2018.04.004.Peer-Reviewed Original ResearchConceptsAlcohol-induced liver injuryAlcoholic hepatitisAlanine aminotransferase levelsLiver injuryNeutrophil influxAminotransferase levelsΒ-hydroxybutyrateDevelopment of AHPlasma alanine aminotransferase levelsGreater neutrophil influxExcess alcohol intakeAlcoholic liver diseaseLife-threatening conditionExcess alcohol consumptionDependent pathwayHigher plasma alanine aminotransferase levelsIntrahepatic macrophagesLiver inflammationLiver diseaseAlcohol intakeHepatoprotective roleReduced steatosisM2 phenotypeTherapeutic effectHepatitis
2017
Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.Peer-Reviewed Original ResearchConceptsLiver injuryInflammatory responseBile acid-induced liver injuryCholestatic liver injuryInflammatory liver injuryProinflammatory cytokine expressionCholestatic liver diseaseBile duct ligationVivo mouse modelHepatic infiltrationInflammatory injurySerum aminotransferasesLiver diseaseCholestatic patientsCytokine expressionChemokine inductionPathophysiologic concentrationsNeutrophil chemotaxisDuct ligationPathophysiologic levelsMouse modelNew therapiesInnate immunityInjuryPeriportal areas
2014
Immune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis
Morales C, Rachidi S, Hong F, Sun S, Ouyang X, Wallace C, Zhang Y, Garret-Mayer E, Wu J, Liu B, Li Z. Immune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis. Cancer Research 2014, 74: 446-459. PMID: 24322981, PMCID: PMC4002507, DOI: 10.1158/0008-5472.can-13-1677.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCell Transformation, NeoplasticColitisColonColonic NeoplasmsCrosses, GeneticCytokinesDisease ProgressionDNA RepairGene DeletionGene Expression Regulation, NeoplasticInflammationInterleukin-17Interleukin-23MacrophagesMaleMembrane GlycoproteinsMiceMice, KnockoutMucous MembraneConceptsDNA repair machineryDNA repair pathwaysColon tumorigenesisTumor-associated macrophagesRepair machineryRepair pathwaysOncogenic programEndoplasmic reticulumMutation rateChaperone gp96Β-cateninColon cancerMechanistic underpinningsCellular sitesTumorigenesisReduced expressionEpithelial cellsGenotoxic natureToll-like receptorsInflammation-associated colon cancerImportant driverGp96Inflammation-associated colon tumorigenesisCritical inflammatory cytokinesExpression
2011
Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response
Malik AF, Hoque R, Ouyang X, Ghani A, Hong E, Khan K, Moore LB, Ng G, Munro F, Flavell RA, Shi Y, Kyriakides TR, Mehal WZ. Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20095-20100. PMID: 22109549, PMCID: PMC3250158, DOI: 10.1073/pnas.1105152108.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsApoptosis Regulatory ProteinsAspirinBiocompatible MaterialsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cluster AnalysisCytoskeletal ProteinsForeign-Body ReactionGiant CellsInflammasomesInflammationInterleukin-1betaMacrophages, PeritonealMembrane MicrodomainsMiceMice, Inbred C57BLMicrospheresNLR Family, Pyrin Domain-Containing 3 ProteinPolymethyl Methacrylate