Featured Publications
Digoxin 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 range
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
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