2022
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park I, Eichmann A, Min W, Zhou J. Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature Communications 2022, 13: 7637. PMID: 36496409, PMCID: PMC9741628, DOI: 10.1038/s41467-022-35262-w.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionThioredoxin 2Single-cell RNA-seq analysisRNA-seq analysisMutant miceNuclear genesMitochondrial proteinsMitochondrial localizationHuman retinal diseasesTranscriptional factorsGene expressionMutant retinasMitochondrial activityExtracellular matrixNovel mechanismVascular maturationArteriovenous malformationsGenetic deficiencyVessel growthSmad2Mouse retinaVascular malformationsMechanistic studiesBasement membraneRetinal vascular malformations
2020
Mural 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
2016
Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation
Zhou HJ, Qin L, Zhang H, Tang W, Ji W, He Y, Liang X, Wang Z, Yuan Q, Vortmeyer A, Toomre D, Fuh G, Yan M, Kluger MS, Wu D, Min W. Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nature Medicine 2016, 22: 1033-1042. PMID: 27548575, PMCID: PMC5014607, DOI: 10.1038/nm.4169.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-1Angiopoietin-2AnimalsApoptosis Regulatory ProteinsBrainEndothelium, VascularEnzyme-Linked Immunosorbent AssayExocytosisFluorescent Antibody TechniqueGene Expression ProfilingHemangioma, Cavernous, Central Nervous SystemHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceNerve Tissue ProteinsProto-Oncogene ProteinsReceptor, TIE-2Vesicle-Associated Membrane Protein 3
2013
A Network of Interactions Enables CCM3 and STK24 to Coordinate UNC13D-Driven Vesicle Exocytosis in Neutrophils
Zhang Y, Tang W, Zhang H, Niu X, Xu Y, Zhang J, Gao K, Pan W, Boggon TJ, Toomre D, Min W, Wu D. A Network of Interactions Enables CCM3 and STK24 to Coordinate UNC13D-Driven Vesicle Exocytosis in Neutrophils. Developmental Cell 2013, 27: 215-226. PMID: 24176643, PMCID: PMC3834565, DOI: 10.1016/j.devcel.2013.09.021.Peer-Reviewed Original ResearchConceptsNeutrophil degranulationAcute innate immune responseIschemia-reperfusion injuryInnate immune responseProtection of kidneyNeutrophil functionImmune responseInhibition of exocytosisTissue damageGranule poolGranule contentsDegranulationImportant regulatorImportant roleVesicle exocytosisExocytosisSTK24InjuryNeutrophilsKidneyUNC13D
2011
Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology
Louvi A, Chen L, Two AM, Zhang H, Min W, Günel M. Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 3737-3742. PMID: 21321212, PMCID: PMC3048113, DOI: 10.1073/pnas.1012617108.Peer-Reviewed Original ResearchConceptsNeural cellsCerebral cavernous malformationsCell-nonautonomous mechanismsPathogenesis of CCMsRho GTPase signalingCell-autonomous mechanismsCell-autonomous roleCerebral cavernous malformation 3Cell death 10Central nervous systemConditional mouse mutantsNonautonomous functionsCytoskeletal remodelingRNA sequencingCCM3/Mouse mutantsNeurovascular unitNonautonomous mechanismsProper developmentVascular lesionsGene 1Function mutationsNervous systemAutonomous mechanismsLate functions
2010
Crystal Structure of CCM3, a Cerebral Cavernous Malformation Protein Critical for Vascular Integrity*
Li X, Zhang R, Zhang H, He Y, Ji W, Min W, Boggon TJ. Crystal Structure of CCM3, a Cerebral Cavernous Malformation Protein Critical for Vascular Integrity*. Journal Of Biological Chemistry 2010, 285: 24099-24107. PMID: 20489202, PMCID: PMC2911348, DOI: 10.1074/jbc.m110.128470.Peer-Reviewed Original ResearchMeSH KeywordsApoptosis Regulatory ProteinsBinding, CompetitiveBrainCrystallography, X-RayDimerizationHemangioma, Cavernous, Central Nervous SystemHumansKineticsMembrane ProteinsMolecular ConformationMutationPaxillinProtein ConformationProtein FoldingProtein Structure, SecondaryProtein Structure, TertiaryProto-Oncogene ProteinsConceptsN-terminal dimerization domainPaxillin LD motifsCerebral cavernous malformationsAlpha-helical proteinsLD motifsCCM complexHomology domainFocal adhesionsDimerization domainMolecular basisHydrophobic pocketHuman populationCCM3 mutationsMutationsCCM3Crystal structureVascular integrityCCM2DomainPaxillinProteinMotifCCM1InteractionCells
2008
AIP1 Is Critical in Transducing IRE1-mediated Endoplasmic Reticulum Stress Response*
Luo D, He Y, Zhang H, Yu L, Chen H, Xu Z, Tang S, Urano F, Min W. AIP1 Is Critical in Transducing IRE1-mediated Endoplasmic Reticulum Stress Response*. Journal Of Biological Chemistry 2008, 283: 11905-11912. PMID: 18281285, PMCID: PMC2335342, DOI: 10.1074/jbc.m710557200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCattleDimerizationDNA-Binding ProteinsEndoplasmic ReticulumEndothelial CellsEnzyme ActivationHumansJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 5Membrane ProteinsMiceMice, KnockoutProtein BindingProtein Serine-Threonine KinasesProtein Structure, TertiaryRas GTPase-Activating ProteinsRegulatory Factor X Transcription FactorsSignal TransductionTranscription FactorsX-Box Binding Protein 1ConceptsASK1-interacting protein-1