2021
CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling
Qin L, Zhang H, Li B, Jiang Q, Lopez F, Min W, Zhou JH. CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling. Arteriosclerosis Thrombosis And Vascular Biology 2021, 41: 2943-2960. PMID: 34670407, PMCID: PMC8613000, DOI: 10.1161/atvbaha.121.316707.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCells, CulturedEndothelial CellsEndothelium, LymphaticFemaleGene DeletionHemangioma, Cavernous, Central Nervous SystemHyperplasiaMaleMAP Kinase Signaling SystemMice, Inbred StrainsModels, AnimalNF-kappa BTranslocation, GeneticVascular Endothelial Growth Factor Receptor-3ConceptsLymphatic ECsLymphatic defectsCerebral cavernous malformationsPan-endothelial cellsGrowth factor receptorTranscriptional levelTransport assaysLymphatic hyperplasiaCCM genesLymphatic dysfunctionNuclear translocationGenesFactor receptorVEGFR3ERK1/2Nuclear factorDeletionEC proliferationInhibition of VEGFR3Dependent mannerVascular endothelial growth factor receptorEndothelial growth factor receptorEC deletionAbnormal valve structureKPNA2Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model
Zhou HJ, Qin L, Jiang Q, Murray KN, Zhang H, Li B, Lin Q, Graham M, Liu X, Grutzendler J, Min W. Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model. Nature Communications 2021, 12: 504. PMID: 33495460, PMCID: PMC7835246, DOI: 10.1038/s41467-020-20774-0.Peer-Reviewed Original ResearchConceptsCerebral cavernous malformationsCCM lesionsSmooth muscle actin-positive pericytesEndothelial cell lossRegions of brainCCM pathogenesisPost-capillary venulesCerebral hemorrhagePharmacological blockadeVascular abnormalitiesEC-specific deletionCavernous malformationsMouse modelCell lossMicrovascular bedGenetic deletionLesion formationLesionsVascular dynamicsBarrier functionMicrovascular structureTwo-photon microscopyTie2PathogenesisMice
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
2017
Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway
Sun Y, Zhang H, Xing X, Zhao Z, He J, Li J, Chen J, Wang M, He Y. Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway. Journal Of Developmental Origins Of Health And Disease 2017, 9: 182-190. PMID: 29110746, DOI: 10.1017/s2040174417000782.Peer-Reviewed Original ResearchConceptsMouse embryosYolk sacHeterozygous mouse embryosGene defectsCCM3 genesPrimary human umbilical vein endothelial cellsLead exposureMitochondrial DNAEmbryonic developmentMtDNA biogenesisMitochondrial morphologyCardiovascular developmentHuman umbilical vein endothelial cellsMitochondrial pathwayGene knockoutEndothelial cellsUmbilical vein endothelial cellsVascular developmentMitochondria pathwayVein endothelial cellsPrimary cellsGenesRNA expressionCell proliferationEmbryos
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