Featured Publications
m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity
Qin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA, Li HB, Ouyang X. m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Reports 2021, 37: 109968. PMID: 34758326, PMCID: PMC8667589, DOI: 10.1016/j.celrep.2021.109968.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseProgression of NAFLDLineage-restricted deletionFatty liver diseaseMultiple mRNA transcriptsMyeloid cell activationDiet-induced developmentMethyladenosine (m<sup>6</sup>A) RNA modificationMRNA metabolismProtein methyltransferaseLiver diseaseRNA modificationsCellular stressMetabolic reprogrammingDDIT4 mRNACell activationObesityDifferential expressionMammalian targetMRNA transcriptsSignificant downregulationCytokine stimulationPathway activityMetabolic phenotypeMRNA levelsDigoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation
Zhao P, Han SN, Arumugam S, Yousaf MN, Qin Y, Jiang JX, Torok NJ, Chen Y, Mankash MS, Liu J, Li J, Iwakiri Y, Ouyang X. Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. AJP Gastrointestinal And Liver Physiology 2019, 317: g387-g397. PMID: 31411894, PMCID: PMC6842989, DOI: 10.1152/ajpgi.00054.2019.Peer-Reviewed Original ResearchConceptsHigh-fat dietSignificant clinical applicabilityHuman nonalcoholic steatohepatitisNonalcoholic steatohepatitisOral digoxinLiver injuryCell subsetsPathway activationMouse modelHigh-fat diet mouse modelLiver injury mouse modelHepatocyte mitochondrial dysfunctionClinical applicabilityDiet mouse modelInjury mouse modelDifferential involvementLarge clinical experienceNLRP3 inflammasome activationSignificant protective effectHIF-1α transactivationHepatic oxidative stress responseHypoxia-inducible factorLiver inflammationHFD miceWide dosage rangeThe DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
Hu B, Jin C, Li HB, Tong J, Ouyang X, Cetinbas NM, Zhu S, Strowig T, Lam FC, Zhao C, Henao-Mejia J, Yilmaz O, Fitzgerald KA, Eisenbarth SC, Elinav E, Flavell RA. The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 2016, 354: 765-768. PMID: 27846608, PMCID: PMC5640175, DOI: 10.1126/science.aaf7532.Peer-Reviewed Original ResearchConceptsCell deathDNA sensor AIM2New therapeutic targetsCaspase-1-dependent deathIntestinal epithelial cellsBone marrow cellsGastrointestinal syndromeTissue injuryInflammasome activationGastrointestinal tractRadiation-induced cell deathRadiation-induced DNA damageTherapeutic targetAcute exposureBone marrowChemotherapeutic agentsMarrow cellsRadiation exposureAIM2Massive cell deathEpithelial cellsHematopoietic failureDeathMolecular mechanismsDNA damageAdenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway
Ouyang X, Ghani A, Malik A, Wilder T, Colegio OR, Flavell RA, Cronstein BN, Mehal WZ. Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway. Nature Communications 2013, 4: 2909. PMID: 24352507, PMCID: PMC3895487, DOI: 10.1038/ncomms3909.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine TriphosphateAnimalsCarrier ProteinsCyclic AMPCyclic AMP Response Element-Binding ProteinCyclic AMP-Dependent Protein KinasesHypoxia-Inducible Factor 1, alpha SubunitInflammasomesInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, Adenosine A2ASignal TransductionConceptsHIF-1α pathwayInflammasome activityInflammasome activationA2A receptorsIL-1β productionIL-1β responseReceptor-mediated signalingLack of responseTolerogenic stateChronic diseasesInflammatory responseInflammasome pathwayPrevious exposureLipopolysaccharideAdenosineReceptorsActivationKey regulatorInitial activationPathwaySignalingResponseInterleukinStimuliDisease
2017
An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization
Park J, Shao M, Kim MY, Baik SK, Cho MY, Utsumi T, Satoh A, Ouyang X, Chung C, Iwakiri Y. An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization. Hepatology 2017, 65: 1720-1734. PMID: 28090670, PMCID: PMC5397326, DOI: 10.1002/hep.29051.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndoplasmic Reticulum StressHumansKupffer CellsLiver Diseases, AlcoholicMaleMice, Inbred C57BLMice, KnockoutNogo ProteinsConceptsAlcoholic liver diseasePositive Kupffer cellsKupffer cellsLiver injuryALD patientsLiver diseaseM1 polarizationKO miceM2 polarizationLieber-DeCarli ethanol liquid dietDisease severityM1/M2 polarizationKupffer cell polarizationEthanol liquid dietHepatic triglyceride levelsM2 macrophage polarizationHigher hepatic triglyceride levelsChronic ethanol feedingNew therapeutic targetsER stressAbsence of NogoM2 statusWT miceM1 activationTriglyceride levels
2016
The SGLT‐2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice
Leng W, Ouyang X, Lei X, Wu M, Chen L, Wu Q, Deng W, Liang Z. The SGLT‐2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice. Mediators Of Inflammation 2016, 2016: 6305735. PMID: 28104929, PMCID: PMC5220517, DOI: 10.1155/2016/6305735.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaApolipoproteins EAtherosclerosisBenzhydryl CompoundsBlood GlucoseBone MarrowDiabetes ComplicationsDiabetes Mellitus, ExperimentalGlucoseGlucosidesInflammasomesInterleukin-18Interleukin-1betaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinReactive Oxygen SpeciesSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsConceptsEffect of dapagliflozinHigh-fat dietIL-1Dapagliflozin treatmentDiabetic atherosclerosisInhibitor dapagliflozinIL-18Reactive oxygen speciesSodium-glucose cotransporter 2 inhibitor dapagliflozinFat metabolismSGLT-2 inhibitor dapagliflozinCaspase-1 pathwayIndices of glucoseHematoxylin-eosin stainingStability of lesionsFormation of atherosclerosisNLRP3 protein levelsOil Red ODiabetic ApoEROS-NLRP3Aortic atherosclerosisMacrophage infiltrationNLRP3 inflammasomeTherapeutic effectMitochondrial reactive oxygen species
2015
Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury
Li M, Mennone A, Soroka CJ, Hagey LR, Ouyang X, Weinman EJ, Boyer JL. Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury. Hepatology 2015, 62: 1227-1236. PMID: 26108984, PMCID: PMC4589453, DOI: 10.1002/hep.27956.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver injuryInflammatory responseICAM-1BDL miceBDL-induced liver injuryNeutrophil-mediated liver injuryTotal bile acid concentrationTumor necrosis factor alphaIntercellular adhesion molecule-1Hepatic neutrophil accumulationAttenuated liver injuryCholestatic liver injuryHepatic inflammatory responseMouse liverSerum alanine aminotransferaseBile acid concentrationsHepatic inflammatory diseasesICAM-1 expressionNecrosis factor alphaAdhesion molecule-1Wild-type miceICAM-1 proteinNew therapeutic targetsMessenger RNA levels
2014
Effect of osteopontin in regulating bone marrow mesenchymal stem cell treatment of skin wounds in diabetic mice
Meng H, Wang Z, Wang W, Li W, Wu Q, Lei X, Ouyang X, Liang Z. Effect of osteopontin in regulating bone marrow mesenchymal stem cell treatment of skin wounds in diabetic mice. Diabetes/Metabolism Research And Reviews 2014, 30: 457-466. PMID: 24827928, DOI: 10.1002/dmrr.2566.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCells, CulturedDiabetes Mellitus, ExperimentalFetal Stem CellsGreen Fluorescent ProteinsMaleMesenchymal Stem Cell TransplantationMesenchymal Stem CellsMice, Inbred C57BLMice, KnockoutMice, TransgenicMicrovesselsNeovascularization, PhysiologicOsteopontinRandom AllocationRecombinant Fusion ProteinsSkinWound HealingWounds, PenetratingConceptsWT mesenchymal stem cellsMesenchymal stem cellsHealing timeNormal miceDiabetic miceSkin woundsBone marrow mesenchymal stem cell treatmentMesenchymal stem cell treatmentStem cellsWestern blottingHealing woundsKO male miceWild-type miceWounds of miceDiabetic skin woundsRole of osteopontinStem cell treatmentEffect of osteopontinExpression of osteopontinBacks of miceDiabetes mellitusIntraperitoneal injectionMale miceMicrovessel densityTail veinActivation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway
Farooq A, Hoque R, Ouyang X, Farooq A, Ghani A, Ahsan K, Guerra M, Mehal WZ. Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway. AJP Gastrointestinal And Liver Physiology 2014, 307: g732-g740. PMID: 25104498, PMCID: PMC4187065, DOI: 10.1152/ajpgi.00073.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsAspartic AcidBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCaspase 1Cell LineChemical and Drug Induced Liver InjuryDisease Models, AnimalExcitatory Amino Acid AgonistsHumansInflammasomesInterleukin-1betaLiverMacrophagesMaleMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinPancreatitisProtein PrecursorsReceptors, N-Methyl-D-AspartateSignal TransductionTime FactorsConceptsNMDA receptorsAcute hepatitisLiver inflammationInflammasome activityAcute inflammatory liver injuryNOD-like receptor familyN-methyl-D-aspartate (NMDA) receptor familyChronic liver inflammationInflammatory liver injuryΒ-arrestinBrain NMDA receptorsReceptor familyNMDA receptor pathwayLigand-gated ion channelsLiver injuryNonalcoholic steatohepatitisImmune suppressionLimits injuryNF-kβImmune regulationInflammasome activationKupffer cellsInflammasome machineryPyrin domainNonneuronal cells
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 MethacrylateTranscription factor IRF8 directs a silencing programme for TH17 cell differentiation
Ouyang X, Zhang R, Yang J, Li Q, Qin L, Zhu C, Liu J, Ning H, Shin MS, Gupta M, Qi CF, He JC, Lira SA, Morse HC, Ozato K, Mayer L, Xiong H. Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation. Nature Communications 2011, 2: 314. PMID: 21587231, PMCID: PMC3112536, DOI: 10.1038/ncomms1311.Peer-Reviewed Original ResearchConceptsTh17 cell differentiationRegulatory factor familyTranscription factor IRF8T cell-specific deletionCritical roleFunctional diversityLineage commitmentTranscription factorsCell-specific deletionFactor familyTranscriptional inhibitorIRF8 geneMolecular mechanismsCell differentiationConventional knockoutIRF8IRF8 deficiencyPhysical interactionDifferentiationTh17 cellsPathogenesis of autoimmunityCellsGenesUnique subsetDiversity
2010
Potentiation of Th17 cytokines in aging process contributes to the development of colitis
Ouyang X, Yang Z, Zhang R, Arnaboldi P, Lu G, Li Q, Wang W, Zhang B, Cui M, Zhang H, Liang-Chen J, Qin L, Zheng F, Huang B, Xiong H. Potentiation of Th17 cytokines in aging process contributes to the development of colitis. Cellular Immunology 2010, 266: 208-217. PMID: 21074754, PMCID: PMC3006034, DOI: 10.1016/j.cellimm.2010.10.007.Peer-Reviewed Original ResearchConceptsT cellsIL-17IL-22Aged miceTh17 cytokinesDendritic cellsYoung miceImmune responseAutoimmune/inflammatory diseasesDevelopment of colitisIL-17 productionMemory T cellsNaïve T cellsSevere colitisIL-17FInflammatory disordersInflammatory diseasesAged individualsMRNA expressionMiceColitisAged peopleSignificant differencesCytokinesHealthy ones
2009
Reduction of Stat3 Activity Attenuates HIV-Induced Kidney Injury
Feng X, Lu TC, Chuang PY, Fang W, Ratnam K, Xiong H, Ouyang X, Shen Y, Levy DE, Hyink D, Klotman M, D'Agati V, Iyengar R, Klotman PE, He JC. Reduction of Stat3 Activity Attenuates HIV-Induced Kidney Injury. Journal Of The American Society Of Nephrology 2009, 20: 2138-2146. PMID: 19608706, PMCID: PMC2754106, DOI: 10.1681/asn.2008080879.Peer-Reviewed Original ResearchConceptsHIV-associated nephropathyPodocyte differentiation markersSTAT3 phosphorylationDevelopment of HIVANPathogenesis of HIVANHIV-1 transgenic miceSTAT3 activityReduced expressionHIV-1 transgeneDifferentiation markersExpression of VEGFTg26 miceKidney injuryTubulointerstitial injuryActivation of STAT3Tubulointerstitial compartmentHIV-1 NefTransgenic miceB cell developmentProliferation markersPodocyte proliferationHuman kidneyMiceSTAT3 target genesPrimary podocytes
2008
Epstein‐Barr virus‐induced gene 3 negatively regulates IL‐17, IL‐22 and RORγt
Yang J, Yang M, Htut TM, Ouyang X, Hanidu A, Li X, Sellati R, Jiang H, Zhang S, Li H, Zhao J, Ting AT, Mayer L, Unkeless JC, Labadia ME, Hodge M, Li J, Xiong H. Epstein‐Barr virus‐induced gene 3 negatively regulates IL‐17, IL‐22 and RORγt. European Journal Of Immunology 2008, 38: 1204-1214. PMID: 18412165, PMCID: PMC2989250, DOI: 10.1002/eji.200838145.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCell DifferentiationForkhead Transcription FactorsGene ExpressionGene Expression RegulationInterferon-gammaInterleukin-17InterleukinsListeria monocytogenesListeriosisMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMinor Histocompatibility AntigensNuclear Receptor Subfamily 1, Group F, Member 3OvalbuminReceptors, Antigen, T-CellReceptors, Retinoic AcidReceptors, Thyroid HormoneSpleenT-LymphocytesT-Lymphocytes, RegulatoryTumor Necrosis Factor-alphaConceptsIL-17IL-22Th17 cellsIL-27Spleen cellsRORgamma tEpstein-Barr virus-induced gene 3IL-17-producing cellsReduced bacterial loadIL-35Protective immunityIL-12p35Th17 conditionsAdaptive immunityEBI3Mouse studiesL. monocytogenesBacterial loadMiceElevated levelsAcute challengeGene 3High levelsP28Immunity