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 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
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 diseaseRNA modifications in the progression of liver diseases: from fatty liver to cancer
Li S, Mehal W, Ouyang X. RNA modifications in the progression of liver diseases: from fatty liver to cancer. Science China Life Sciences 2024, 67: 2105-2119. PMID: 38809498, PMCID: PMC11545962, DOI: 10.1007/s11427-023-2494-x.Peer-Reviewed Original ResearchRNA modificationsRNA metabolismRNA speciesNon-alcoholic fatty liver diseaseN1-methyladenosineCellular functionsN6-methyladenosineGene expressionRNANon-alcoholic steatohepatitisFatty liver to non-alcoholic steatohepatitisM6AHepatocellular carcinomaGlobal health concernFatty liver diseaseLiver diseaseM5CHigher risk of metabolic syndromePseudouridineAssociated with higher risk of metabolic syndromePathological conditionsRisk of metabolic syndromeGenes-methyladenosineProgression of liver disease
2019
The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus.
Leng W, Wu M, Pan H, Lei X, Chen L, Wu Q, Ouyang X, Liang Z. The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus. Annals Of Translational Medicine 2019, 7: 429. PMID: 31700865, PMCID: PMC6803170, DOI: 10.21037/atm.2019.09.03.Peer-Reviewed Original ResearchHFD/streptozotocinHigh-fat dietDiabetes mellitusExperimental steatohepatitisHepatic damageNOD-like receptor family pyrin domainSodium-glucose cotransporter 2 inhibitorsGlucose cotransporter 2 inhibitorsDiabetic liver injuryEfficacy of dapagliflozinROS-NLRP3 inflammasomeSGLT2 inhibitor dapagliflozinHepatic reactive oxygen speciesCotransporter 2 inhibitorsReactive oxygen speciesFamily pyrin domainHepatic lipid accumulationSterile inflammatory responseMajor clinical consequencesDAPA treatmentDM patientsInhibitor dapagliflozinLiver injuryLiver diseaseLiver steatosis
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
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
Hepatocyte 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