Featured Publications
Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation
Arumugam S, Li B, Boodapati S, Nathanson M, Sun B, Ouyang X, Mehal W. Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation. Hepatology 2023, 78: 1448-1461. PMID: 37013923, PMCID: PMC10804318, DOI: 10.1097/hep.0000000000000388.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelBioenergetic capacityMitochondrial DNATranscriptional upregulationCyclic GMP-AMP synthaseGMP-AMP synthaseTranscriptional regulationBioenergetic organellesFunctional mitochondriaMitochondrial membraneExternal mitochondrial membraneAnabolic pathwaysMitochondrial massAnion channelInterferon genesHSC transdifferentiationSubsequent activationCGAS-STINGTransdifferentiationIRF3 pathwayPathwaySTING pathwayGenesMitochondriaQuiescent HSCsDigoxin 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 rangeDigoxin 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
2023
New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders
Jamshed F, Dashti F, Ouyang X, Mehal W, Banini B. New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders. World Journal Of Gastroenterology 2023, 29: 1824-1837. PMID: 37032732, PMCID: PMC10080697, DOI: 10.3748/wjg.v29.i12.1824.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2022
Digoxin as an emerging therapy in noncardiac diseases
Dashti F, Jamshed F, Ouyang X, Mehal W, Banini B. Digoxin as an emerging therapy in noncardiac diseases. Trends In Pharmacological Sciences 2022, 44: 199-203. PMID: 36396496, DOI: 10.1016/j.tips.2022.10.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface
Zhao N, Zhang X, Ding J, Pan Q, Zheng MH, Liu WY, Luo G, Qu J, Li M, Li L, Cheng Y, Peng Y, Xie Q, Wei Q, Li Q, Zou L, Ouyang X, Cai SY, Boyer JL, Chai J. SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface. JCI Insight 2022, 7: e154113. PMID: 35938531, PMCID: PMC9462498, DOI: 10.1172/jci.insight.154113.Peer-Reviewed Original ResearchConceptsIntegrin β1Lipid accumulationPrimary mouse hepatocytesProtein interactionsLipid droplet accumulationMouse liverFatty acid oxidationHeterozygous mutationsIntegrin β1 proteinPKC-α phosphorylationFA uptakeGenetic determinantsMouse peritoneal macrophagesCell membraneStrong genetic determinantsMutationsMouse hepatocytesDroplet accumulationΒ1 proteinCD36 expressionAcid oxidationPKCTriglyceride synthesisGenetic polymorphismsAccumulationAnnexin A2: The diversity of pathological effects in tumorigenesis and immune response
Huang Y, Jia M, Yang X, Han H, Hou G, Bi L, Yang Y, Zhang R, Zhao X, Peng C, Ouyang X. Annexin A2: The diversity of pathological effects in tumorigenesis and immune response. International Journal Of Cancer 2022, 151: 497-509. PMID: 35474212, DOI: 10.1002/ijc.34048.Peer-Reviewed Original ResearchConceptsImmune responseAnnexin A2Pathological effectsToll-like receptor 2Anti-dsDNA antibodiesAcute promyelocytic leukemiaImmune host responseVariety of tumorsEpithelial-mesenchymal transitionInhibition of invasionTumor drug resistanceMultiple tumor cellsInflammatory factorsPathophysiologic processesG1-S phaseRetinal angiogenesisPromyelocytic leukemiaReceptor 2Production of plasminTumor cell invasionHost responseMultiple signal pathwaysNumerous malignanciesDrug resistanceTumor cellsRevisiting the Principles of Preservation in an Era of Pandemic Obesity
Langford JT, DiRito JR, Doilicho N, Chickering GR, Stern DA, Ouyang X, Mehal W, Tietjen GT. Revisiting the Principles of Preservation in an Era of Pandemic Obesity. Frontiers In Immunology 2022, 13: 830992. PMID: 35432296, PMCID: PMC9011385, DOI: 10.3389/fimmu.2022.830992.Peer-Reviewed Original ResearchConceptsDeceased donorsOrgan preservationDonor populationIschemia-reperfusion injuryCurrent obesity epidemicHealthy donor populationPandemic obesityObese donorsReperfusion injuryMetabolic dysfunctionObesity epidemicObesitySignificant declineOrgansDonorsPopulationCurrent practiceDysfunctionTransplantInjury
2019
Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse
Cai SY, Ge M, Mennone A, Hoque R, Ouyang X, Boyer JL. Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse. Cellular And Molecular Gastroenterology And Hepatology 2019, 9: 679-688. PMID: 31887435, PMCID: PMC7160576, DOI: 10.1016/j.jcmgh.2019.12.008.Peer-Reviewed Original ResearchConceptsWT BDL miceCholestatic liver injuryBDL liversBDL miceBile duct ligationBile acidsLiver injuryCholestatic patientsIL-1βM2 anti-inflammatory macrophagesPrimary sclerosing cholangitisPlasma IL-1βLiver hydroxyproline contentLiver of patientsPrimary biliary cholangitisHealthy control subjectsCD206-positive cellsAnti-inflammatory macrophagesIL-1β inductionEndogenous bile acidsCaspase-1 cleavageProcaspase-1 cleavageMouse hepatocytesSclerosing cholangitisLiver histologyThe 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
2018
The multi-dimensional role of intestinal HIFs in liver pathobiology
Ouyang X, Mehal WZ. The multi-dimensional role of intestinal HIFs in liver pathobiology. Journal Of Hepatology 2018, 69: 772-773. PMID: 30104025, DOI: 10.1016/j.jhep.2018.07.012.Peer-Reviewed Original Research
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
2015
Identification 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
Activation 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
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 structureSurgeryHypertensionInflammasome biology in fibrogenesis
Ouyang X, Ghani A, Mehal WZ. Inflammasome biology in fibrogenesis. Biochimica Et Biophysica Acta 2013, 1832: 979-988. PMID: 23562491, DOI: 10.1016/j.bbadis.2013.03.020.Peer-Reviewed Original ResearchConceptsInflammatory pathwaysInflammatory responseTissue injuryToll-like receptor agonistsAssociation of TGFPro-fibrotic pathwaysDownstream inflammatory cytokinesCytokines interleukin-1βAcute inflammatory responseTumor necrosis factorLiver stellate cellsNew therapeutic targetsNumber of organsTissue macrophage populationsIL-18Inflammatory cytokinesInterleukin-1βReceptor agonistFibrogenic responseImmune cellsNecrosis factorSterile insultsStellate cellsTherapeutic targetMacrophage populations
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
IFN Regulatory Factor 8 Sensitizes Soft Tissue Sarcoma Cells to Death Receptor–Initiated Apoptosis via Repression of FLICE-like Protein Expression
Yang D, Wang S, Brooks C, Dong Z, Schoenlein PV, Kumar V, Ouyang X, Xiong H, Lahat G, Hayes-Jordan A, Lazar A, Pollock R, Lev D, Liu K. IFN Regulatory Factor 8 Sensitizes Soft Tissue Sarcoma Cells to Death Receptor–Initiated Apoptosis via Repression of FLICE-like Protein Expression. Cancer Research 2009, 69: 1080-1088. PMID: 19155307, PMCID: PMC2633427, DOI: 10.1158/0008-5472.can-08-2520.Peer-Reviewed Original ResearchAnimalsApoptosisCASP8 and FADD-Like Apoptosis Regulating ProteinCaspase 8Caspase InhibitorsCell Line, TumorEnzyme ActivationFas Ligand ProteinHumansImmunohistochemistryInterferon Regulatory FactorsMiceMitochondriaReceptors, TNF-Related Apoptosis-Inducing LigandRNA, MessengerRNA, Small InterferingSarcomaSarcoma, ExperimentalTNF-Related Apoptosis-Inducing Ligand