2023
FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome
Chen M, Cavinato C, Hansen J, Tanaka K, Ren P, Hassab A, Li D, Youshao E, Tellides G, Iyengar R, Humphrey J, Schwartz M. FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: e132-e150. PMID: 36994727, PMCID: PMC10133209, DOI: 10.1161/atvbaha.123.319120.Peer-Reviewed Original ResearchConceptsContractile gene expressionSmooth muscle cellsGene expressionMgR miceWild-type smooth muscle cellsMarfan miceAortic aneurysmMouse modelMarfan syndromeMouse aortic smooth muscle cellsPathogenesis of TAACytoplasmic domainVascular smooth muscle cellsThoracic aortic aneurysmAortic smooth muscle cellsCultured smooth muscle cellsNF-kB activationNF-kB inhibitionMolecular mechanismsIntegrin α2ECM remodelingElastic fiber integrityPhenotypic modulationMarfan's aneurysmsMgR/
2021
Developmental Perspectives on Arterial Fate Specification
Chen D, Schwartz MA, Simons M. Developmental Perspectives on Arterial Fate Specification. Frontiers In Cell And Developmental Biology 2021, 9: 691335. PMID: 34249941, PMCID: PMC8269928, DOI: 10.3389/fcell.2021.691335.Peer-Reviewed Original ResearchVascular morphogenesisStress-induced cell cycle arrestPostnatal retinal angiogenesisKey molecular mechanismsArterial fateCell cycle arrestArterial specificationFate specificationVenous fateMolecular regulatorsMolecular mechanismsCycle arrestDorsal aortaMorphogenesisDevelopmental settingsRecent findings
2020
Integrin-mediated adhesions in regulation of cellular senescence
Shin EY, Park JH, You ST, Lee CS, Won SY, Park JJ, Kim HB, Shim J, Soung NK, Lee OJ, Schwartz MA, Kim EG. Integrin-mediated adhesions in regulation of cellular senescence. Science Advances 2020, 6: eaay3909. PMID: 32494696, PMCID: PMC7202880, DOI: 10.1126/sciadv.aay3909.Peer-Reviewed Original ResearchConceptsClathrin-mediated endocytosisCellular senescenceG protein-coupled receptor kinasesProtein-coupled receptor kinasesElevated reactive oxygen species (ROS) productionIntegrin-mediated adhesionIntegrin endocytosisAmphiphysin 1Exchange factorReactive oxygen species productionReceptor kinaseOxygen species productionMolecular mechanismsCalpain cleavageSenescenceCell adhesionDirect competitionHuman fibroblastsGIT levelsSpecies productionΒPixNew therapeutic directionIntegrinsEndocytosisCentral roleEndothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis
Chen PY, Schwartz MA, Simons M. Endothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis. Frontiers In Cardiovascular Medicine 2020, 7: 53. PMID: 32478094, PMCID: PMC7232582, DOI: 10.3389/fcvm.2020.00053.Peer-Reviewed Original ResearchVascular inflammationMesenchymal transitionBiology of atherosclerosisPotential new therapeutic targetChronic progressive diseaseNew therapeutic targetsSelective inflammatory mediatorsProgressive diseaseInflammatory mediatorsAtherosclerotic plaquesBlood flowTherapeutic targetPlaque growthInflammationAtherosclerosisMultiple attemptsDiseaseMolecular mechanismsEndMTPlaques
2016
Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling
Yun S, Budatha M, Dahlman JE, Coon BG, Cameron RT, Langer R, Anderson DG, Baillie G, Schwartz MA. Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling. Nature Cell Biology 2016, 18: 1043-1053. PMID: 27595237, PMCID: PMC5301150, DOI: 10.1038/ncb3405.Peer-Reviewed Original ResearchConceptsInflammatory signalingIntegrin α5Enhanced phosphodiesterase activityExtracellular matrix remodellingModulates inflammationTherapeutic targetInflammationProstacyclin secretionLipid metabolismEndothelial cellsMatrix remodellingVivo knockdownECM remodellingBasement membraneIntegrin α2Phosphodiesterase activityMolecular mechanismsRemodellingΑ5Direct bindingSignalingCellsFibronectinAtherosclerosisArtery
2013
Integrins in mechanotransduction
Ross TD, Coon BG, Yun S, Baeyens N, Tanaka K, Ouyang M, Schwartz MA. Integrins in mechanotransduction. Current Opinion In Cell Biology 2013, 25: 613-618. PMID: 23797029, PMCID: PMC3757118, DOI: 10.1016/j.ceb.2013.05.006.Peer-Reviewed Original ResearchConceptsMolecular mechanismsIntegrin-mediated adhesionImportant regulatory eventActin cytoskeletonRegulatory eventsExtracellular matrixNormal physiologyCell functionMajor insightsCentral roleCellsRecent advancesCytoskeletonEffect of forceMechanotransductionAdhesionIntegrinsPathwayPhysiologyMechanismRecent work
2012
Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment
Yaqoob U, Cao S, Shergill U, Jagavelu K, Geng Z, Yin M, de Assuncao TM, Cao Y, Szabolcs A, Thorgeirsson S, Schwartz M, Yang JD, Ehman R, Roberts L, Mukhopadhyay D, Shah VH. Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment. Cancer Research 2012, 72: 4047-4059. PMID: 22738912, PMCID: PMC3421041, DOI: 10.1158/0008-5472.can-11-3907.Peer-Reviewed Original ResearchConceptsFibronectin fibril assemblyTumor growthTumor microenvironmentNeuropilin-1Fibril assemblyStromal myofibroblastsNonreceptor tyrosine kinase c-AblTyrosine kinase c-AblHuman cancer specimensNew molecular mechanismCancer cell invasionNRP-1 levelsSerine 612Intracellular associationExtracellular domainMatrix stiffnessMolecular mechanismsC-AblGenetic depletionMatrix proteinsCell invasionClinical outcomesCancer specimensTherapeutic targetingAntibody neutralization
2005
Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization
del Pozo MA, Balasubramanian N, Alderson NB, Kiosses WB, Grande-García A, Anderson RG, Schwartz MA. Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nature Cell Biology 2005, 7: 901-908. PMID: 16113676, PMCID: PMC1351395, DOI: 10.1038/ncb1293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaveolaeCaveolin 1CaveolinsCell AdhesionCell ProliferationDynamin IIEndocytosisExtracellular MatrixExtracellular Signal-Regulated MAP KinasesFocal AdhesionsIntegrinsMembrane MicrodomainsMiceMice, KnockoutMicroscopy, Electron, TransmissionNeoplasm InvasivenessNeoplasmsNIH 3T3 CellsPhosphatidylinositol 3-KinasesPhosphorylationRac GTP-Binding ProteinsConceptsCaveolin-1Cholesterol-enriched membrane microdomainsPhosphatidylinositol-3-OH kinaseCell detachmentNovel molecular mechanismCholesterol-rich domainsInhibition of ERKMembrane microdomainsFocal adhesionsDynamin 2Plasma membraneMolecular mechanismsTumor suppressionTyr-14Multiple pathwaysNormal cellsInternalizationERKRacPathwayCaveolaeKinasePhosphorylationAdhesionMicrodomainsIntegrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch*
Katsumi A, Naoe T, Matsushita T, Kaibuchi K, Schwartz MA. Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch*. Journal Of Biological Chemistry 2005, 280: 16546-16549. PMID: 15760908, DOI: 10.1074/jbc.c400455200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionEnzyme ActivationEnzyme InhibitorsExtracellular MatrixExtracellular Signal-Regulated MAP KinasesIntegrin alphaVbeta3IntegrinsJNK Mitogen-Activated Protein KinasesLigandsMAP Kinase Kinase 4MiceMitogen-Activated Protein Kinase KinasesNIH 3T3 CellsPhosphatidylinositol 3-KinasesPhosphorylationProtein ConformationSignal TransductionStress, MechanicalTime FactorsConceptsIntegrin activationExtracellular matrix proteinsRole of integrinsConformational activationBiochemical signalsNIH3T3 cellsMolecular mechanismsCellular responsesMatrix proteinsExtracellular matrixCell growthMechanical stretch stimulationIntegrin alphavbeta3IntegrinsMechanical tensionMechanical stretchCritical determinantStretch stimulationActivationPhosphoinositolMechanotransductionJNKProteinApoptosisDifferentiation