2024
SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling
Xu Y, Zhang H, Chen Y, Pober J, Zhou M, Zhou J, Min W. SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling. Nature Communications 2024, 15: 6919. PMID: 39134547, PMCID: PMC11319592, DOI: 10.1038/s41467-024-51350-5.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSerum response factorCardiovascular diseaseVSMC synthetic phenotypeVascular remodelingNeointimal formationSENP1 deficiencySerum response factor activitySmooth muscle phenotypic switchingPhenotypic switchingPathogenesis of cardiovascular diseaseSmooth muscle cellsPost-translational SUMOylationTreatment of cardiovascular diseasesInhibitor AZD6244Phospho-ELK1Increased nuclear accumulationLysosomal localizationGene transcriptionNuclear accumulationMuscle cellsCoronary arteryCVD patientsVSMC phenotypic switchTherapeutic potential
2020
Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance
He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. Journal Of Experimental Medicine 2020, 218: e20201416. PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAnimalsDiabetes Mellitus, Type 2Diet, High-FatEnergy MetabolismFatty LiverGene DeletionGene TargetingGluconeogenesisHomeostasisHumansHyperglycemiaInflammationInsulin ResistanceLipogenesisLiverMaleMice, Inbred C57BLMice, KnockoutMitochondriaMitophagyNF-kappa BOxidative StressPhenotypeReactive Oxygen SpeciesSequestosome-1 ProteinSignal TransductionThioredoxinsConceptsHepatic insulin resistanceWhite adipose tissueInsulin resistanceAdipose inflammationType 2 diabetes mellitusLipid metabolic disordersNF-κB inhibitorAdipose-specific deletionWhole-body energy homeostasisAltered fatty acid metabolismFatty acid metabolismT2DM progressionT2DM patientsDiabetes mellitusReactive oxygen species pathwayHepatic steatosisMetabolic disordersNF-κBP62/SQSTM1Adipose tissueHuman adipocytesEnergy homeostasisExcessive mitophagyOxygen species pathwayInflammationMural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations
Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/atvbaha.120.314586.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBrainCell CommunicationCell MovementCells, CulturedCoculture TechniquesEndothelial CellsFemaleFocal AdhesionsGene DeletionGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMaleMembrane ProteinsMice, KnockoutMicrovesselsMyocytes, Smooth MusclePaxillinPericytesPhenotypeProtein StabilityProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsBrain mural cellsCCM lesionsMural cellsCavernous malformationsSevere brain hemorrhageCCM pathogenesisSmooth muscle cellsWeeks of ageCell-specific deletionMural cell coverageBrain pericytesBrain hemorrhageNeonatal stageBrain vasculatureLesionsEntire brainMuscle cellsCerebral cavernous malformation 3Endothelial cellsMicePericytesSpecific deletionAdhesion formationPathogenesis
2019
Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome
Yang B, Huang Y, Zhang H, Huang Y, Zhou HJ, Young L, Xiao H, Min W. Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome. Journal Of Molecular And Cellular Cardiology 2019, 138: 291-303. PMID: 31751569, DOI: 10.1016/j.yjmcc.2019.10.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBradycardiaCardiomyopathy, DilatedEnhancer Elements, GeneticHistone DeacetylasesHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMEF2 Transcription FactorsMice, KnockoutMitochondria, HeartModels, BiologicalOxidative StressPhenotypeProtein BindingReactive Oxygen SpeciesRNA, MessengerSick Sinus SyndromeSinoatrial NodeThioredoxinsConceptsSick sinus syndromeSinus syndromeHistone deacetylase 4Lower heart rateHeart rateHCN4 expressionConduction systemSinoatrial nodeNormal heart rateCardiac conduction systemHistone 3 acetylationMitochondrial oxidative stressSinus bradycardiaCardiac functionLox/SyndromeHeart rhythmMyosin heavy chainHistological analysisMiceDeletion miceOxidative stressWhole heartProtein levelsUnderlying mechanismCCM3 and cerebral cavernous malformation disease
Wang K, Zhou HJ, Min W. CCM3 and cerebral cavernous malformation disease. Stroke And Vascular Neurology 2019, 4: svn-2018-000195. PMID: 31338212, PMCID: PMC6613868, DOI: 10.1136/svn-2018-000195.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCapillary PermeabilityCell MovementCell ProliferationCerebral ArteriesEndothelial CellsGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMembrane ProteinsMutationNeovascularization, PathologicPhenotypeProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsSmall blood vesselsTreatment of CCMsCerebral cavernous malformation diseaseBlood vesselsRisk of strokeUnique biological functionsPotential therapeutic strategyFocal neurological defectsCCM proteinsEndothelial cell junctionsCCM3/Vascular lesionsBiological functionsDifferent genesCCM genesCavernous malformationsSevere formTherapeutic strategiesCell junctionsNeurological defectsSimilar functionsMalformation diseaseCCM diseaseDisease
2015
SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression
Shao L, Zhou HJ, Zhang H, Qin L, Hwa J, Yun Z, Ji W, Min W. SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression. Nature Communications 2015, 6: 8917. PMID: 26596471, PMCID: PMC4662081, DOI: 10.1038/ncomms9917.Peer-Reviewed Original ResearchMeSH Keywords3T3-L1 CellsAdipocytesAnimalsApoptosisChemokine CCL5Chromatin ImmunoprecipitationCysteine EndopeptidasesCytokinesDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2Diet, High-FatEndopeptidasesEnzyme-Linked Immunosorbent AssayFlow CytometryGene Knockout TechniquesGlucose IntoleranceHyperglycemiaImmunoblottingImmunoprecipitationInflammationInsulin ResistanceInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsIslets of LangerhansMiceMutagenesis, Site-DirectedNF-kappa BPhenotypeReverse Transcriptase Polymerase Chain ReactionSmall Ubiquitin-Related Modifier ProteinsConceptsNF-κB activityAdipocyte dysfunctionCytokine productionType 1 diabetes progressionPancreatic isletsType 1 diabetes mellitusMild insulin resistanceDevelopment of diabetesType 2 diabetes phenotypeΒ-cell damageDirect cytotoxic effectNF-κB inhibitorAdipocyte-specific deletionProgression of T1DMDiabetes mellitusGlucose intolerancePancreatic inflammationProinflammatory cytokinesCCL5 expressionInsulin resistanceDiabetes progressionInflammatory responseNF-κBDiabetes phenotypeMice exhibit