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 rangeAdenosine 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
2024
Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population
Ding J, Liu H, Zhang X, Zhao N, Peng Y, Shi J, Chen J, Chi X, Li L, Zhang M, Liu W, Zhang L, Ouyang J, Yuan Q, Liao M, Tan Y, Li M, Xu Z, Tang W, Xie C, Li Y, Pan Q, Xu Y, Cai S, Byrne C, Targher G, Ouyang X, Zhang L, Jiang Z, Zheng M, Sun F, Chai J. Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population. Science Translational Medicine 2024, 16: eadh9940. PMID: 39504356, DOI: 10.1126/scitranslmed.adh9940.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseWhole-genome sequencingHepatocellular carcinomaMolecular subtypesLiver cirrhosisChinese cohort of patientsInfiltration of M1Risk of liver cirrhosisSerum metabolic analysisClinical diagnosisSubtype of nonalcoholic fatty liver diseaseCohort of patientsDevelopment of liver cirrhosisHepatocellular carcinoma developmentIntegrative multiomic analysisHealth care burdenFatty liver diseaseExpression of CYP1A2Urine specimensTreatment strategiesChinese cohortImpaired outcomeM2 macrophagesIntegrative multiomicsLiver disease
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
2019
The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot Ulcer
Wu M, Leng W, Pan H, Lei X, Chen L, Ouyang X, Liang Z. The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot Ulcer. Mediators Of Inflammation 2019, 2019: 6705424. PMID: 31007603, PMCID: PMC6441532, DOI: 10.1155/2019/6705424.Peer-Reviewed Original ResearchConceptsDiabetic foot ulcersCourse of diseaseInterleukin-6Diabetes mellitusFoot ulcersWound groupChronic diabetic foot ulcersChronic wound groupsReduced expressionUncontrolled chronic inflammationRelevant clinical dataExpression of NFResults of immunofluorescenceChronic inflammationInflammatory pathwaysIntractable complicationClinical dataImmunohistochemical stainingRefractory woundsInflammatory regulationInflammationUlcersPatientsAW groupUncontrolled activation
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 ResearchConceptsAlcoholic 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 levelsBile 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
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 speciesHepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9
Garcia-Martinez I, Santoro N, Chen Y, Hoque R, Ouyang X, Caprio S, Shlomchik MJ, Coffman RL, Candia A, Mehal WZ. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. Journal Of Clinical Investigation 2016, 126: 859-864. PMID: 26808498, PMCID: PMC4767345, DOI: 10.1172/jci83885.Peer-Reviewed Original ResearchConceptsDevelopment of NASHNonalcoholic steatohepatitisTLR9 pathwayTLR9 pathway activationCommon liver diseaseObesity-induced changesHigh-fat dietActivation of TLR9Progressive diseaseLiver diseaseInflammatory phenotypeTLR9 antagonistTLR9Animal modelsPlasma mtDNAHepatocyte originPathway activationSteatohepatitisDiseaseMiceCellular requirementsActivationActivation capacityHigh levelsCirrhosis
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 levelsIdentification of a novel de novo GATA3 mutation in a patient with HDR syndrome
Chen L, Chen B, Leng W, Lui X, Wu Q, Ouyang X, Liang Z. Identification of a novel de novo GATA3 mutation in a patient with HDR syndrome. Journal Of International Medical Research 2015, 43: 718-724. PMID: 26268891, DOI: 10.1177/0300060515591065.Peer-Reviewed Original ResearchConceptsHDR syndromeUrea nitrogen levelsNovel de novo mutationRenal dysplasia (HDR) syndromeHaploinsufficiency of GATA3Serum creatinineIntracranial calcificationsLimb twitchesGATA3 mutationsSensorineural deafnessDysplasia syndromeDe novo mutationsSyndromeGATA3 genePatientsPremature stop codonNovo mutationsDeafnessFurther evidenceFrameshift mutationExon 2MutationsHyperphosphataemiaHypoparathyroidismProteinuria
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 cellsImmune 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
2013
Effect of laparoscopic Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus with hypertension: A randomized controlled trial
Liang Z, Wu Q, Chen B, Yu P, Zhao H, Ouyang X. Effect of laparoscopic Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus with hypertension: A randomized controlled trial. Diabetes Research And Clinical Practice 2013, 101: 50-56. PMID: 23706413, DOI: 10.1016/j.diabres.2013.04.005.Peer-Reviewed Original ResearchConceptsType 2 diabetes mellitusGastric bypass surgeryUsual careGroup CLaparoscopic RouxRYGB surgeryBypass surgeryDiabetes mellitusGroup ACardiac structure/functionDiabetes remissionExenatide therapyHypertensive peopleInflammation indexAntihypertensive drugsObese T2DMInflammatory cytokinesMetabolic panelCardiovascular functionGroup BMetabolic parametersObese peopleCardiac structureSurgeryHypertension
2011
Transcription 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