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 ResearchMeSH KeywordsAnimalsAortic Aneurysm, ThoracicFibrillin-1FibronectinsIntegrin alpha5Marfan SyndromeMiceNF-kappa BSwineConceptsContractile 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/
2022
Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes.
Chen M, Hu R, Cavinato C, Zhuang ZW, Zhang J, Yun S, Fernandez Tussy P, Singh A, Murtada SI, Tanaka K, Liu M, Fernández-Hernando C, Humphrey JD, Schwartz MA. Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes. Diabetes 2022, 71: 2020-2033. PMID: 35771994, PMCID: PMC9450851, DOI: 10.2337/db21-0958.Peer-Reviewed Original ResearchConceptsVascular complicationsInjection of streptozotocinBlood flow recoveryHigh-fat dietType 1 diabetesInflammatory cell invasionIntegrin α5T1D miceVascular basement membraneVascular diseaseCarotid arteryHindlimb ischemiaMetalloproteinase expressionMain receptorType 1Plaque sizeBeneficial effectsEndothelial cellsMajor causeCell invasionExtracellular matrix proteinsHyperlipidemiaComplicationsBasement membraneT1D
2021
Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling
Budatha M, Zhang J, Schwartz MA. Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling. Journal Of The American Heart Association 2021, 10: e021160. PMID: 34472370, PMCID: PMC8649308, DOI: 10.1161/jaha.121.021160.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionPathological vascular remodelingVascular remodelingCarotid ligation modelPartial carotid ligation modelAortic constrictionInflammatory activationEndothelial cellsLigation modelArtery wall hypertrophyTransverse aortic constriction (TAC) modelHigh-fat dietIntegrin α5Aortic constriction modelWild-type miceBasement membranePartial carotid ligationVascular endothelial cellsProvisional matrix proteinsAcute atherosclerosisHyperlipidemic ApoEInflammatory markersLigation surgeryWall hypertrophyAcute model
2018
hMENA isoforms impact NSCLC patient outcome through fibronectin/β1 integrin axis
Di Modugno F, Spada S, Palermo B, Visca P, Iapicca P, Di Carlo A, Antoniani B, Sperduti I, Di Benedetto A, Terrenato I, Mottolese M, Gandolfi F, Facciolo F, Chen EI, Schwartz MA, Santoni A, Bissell MJ, Nisticò P. hMENA isoforms impact NSCLC patient outcome through fibronectin/β1 integrin axis. Oncogene 2018, 37: 5605-5617. PMID: 29907768, PMCID: PMC6193944, DOI: 10.1038/s41388-018-0364-3.Peer-Reviewed Original ResearchConceptsCell lung cancer patientsNSCLC patient outcomeFavorable clinical outcomeLung cancer patientsMechanism of actionClinical outcomesCancer patientsStromal fibronectinClinical managementTranscription factor 1Patient outcomesPatient riskΒ1 integrin expressionIntegrin axisNuclear expressionIntegrin expressionCell invasivenessCancer cellsFibronectin productionExtracellular matrix componentsFactor 1G-actin/F-actin ratioΒ1 integrin activationΒ1 integrin ligandsHMenaInhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis
Budatha M, Zhang J, Zhuang ZW, Yun S, Dahlman JE, Anderson DG, Schwartz MA. Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis. Journal Of The American Heart Association 2018, 7: e007501. PMID: 29382667, PMCID: PMC5850249, DOI: 10.1161/jaha.117.007501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesAtherosclerosisCyclic Nucleotide Phosphodiesterases, Type 4Disease Models, AnimalExtracellular MatrixFibronectinsFibrosisGenetic Predisposition to DiseaseHindlimbInflammation MediatorsIntegrin alpha2Integrin alpha5IschemiaLeukocytesMaleMatrix MetalloproteinasesMice, Inbred C57BLMice, Knockout, ApoEMuscle, SkeletalNeovascularization, PhysiologicNF-kappa BPhenotypePlaque, AtheroscleroticSignal TransductionVascular RemodelingConceptsEndothelial inflammatory activationAtherosclerotic plaque sizeInflammatory activationPlaque stabilityVascular remodelingEndothelial NF-κB activationSmooth muscle cell contentPlaque sizeFemoral artery ligationMuscle cell contentTreatment of atherosclerosisInflammatory gene expressionPotential therapeutic targetFibrous cap thicknessNF-κB activationSmaller atherosclerotic plaquesArtery ligationAortic rootHindlimb ischemiaCompensatory remodelingAtherosclerotic plaquesTherapeutic targetLeukocyte contentMetalloproteinase expressionEndothelial basement membrane
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 bindingSignalingCellsFibronectinAtherosclerosisArteryForce regulated conformational change of integrin αVβ3
Chen Y, Lee H, Tong H, Schwartz M, Zhu C. Force regulated conformational change of integrin αVβ3. Matrix Biology 2016, 60: 70-85. PMID: 27423389, PMCID: PMC5237428, DOI: 10.1016/j.matbio.2016.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomechanical PhenomenaBiotinylationCell AdhesionCell LineEndothelial CellsErythrocytesExtracellular MatrixFibronectinsGene ExpressionGlassHumansIntegrin alphaVbeta3KineticsLungMiceMolecular ProbesPoint MutationProtein BindingProtein ConformationSignal TransductionSingle Molecule ImagingConceptsConformational changesTransduce signalsSingle-molecule levelIntegrin functionBiomembrane force probeMolecular machinesPhysiological functionsCell adhesionCell surfaceExtracellular matrixPoint mutationsConformational transitionIntegrinsEssential roleTumor metastasisExtended conformationConformationDynamic equilibriumEctodomainMutationsForce probePhagocytosisMembraneAngiogenesisFunction
2014
Integrin adjunct therapy for melanoma
Andarawewa KL, Moissoglu K, Lee C, Ando Y, Yu M, Debnath P, Shannon JD, Sirinivasan S, Conaway MR, Weber MJ, Schwartz MA. Integrin adjunct therapy for melanoma. Pigment Cell & Melanoma Research 2014, 28: 114-116. PMID: 25264294, PMCID: PMC6542633, DOI: 10.1111/pcmr.12320.Peer-Reviewed Original Research
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 neutralizationThe role of p21-activated kinase in the initiation of atherosclerosis
Jhaveri K, Debnath P, Chernoff J, Sanders J, Schwartz M. The role of p21-activated kinase in the initiation of atherosclerosis. BMC Cardiovascular Disorders 2012, 12: 55. PMID: 22824149, PMCID: PMC3489605, DOI: 10.1186/1471-2261-12-55.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesAtherosclerosisBiomechanical PhenomenaCells, CulturedDisease Models, AnimalEndothelial CellsFibronectinsGalectin 3ImmunohistochemistryInflammation MediatorsIntercellular Adhesion Molecule-1MaleMiceMice, Inbred C57BLMice, KnockoutP21-Activated KinasesRegional Blood FlowTranscription Factor RelBVascular Cell Adhesion Molecule-1ConceptsLesser curvatureNF-κB subunitsInflammatory activationEndothelial cellsAtherosclerosis-prone sitesPro-inflammatory functionsInflammatory marker expressionNormal chow dietArch of aortaInitiation of atherosclerosisInflammatory markersOverall inflammationChow dietInflammatory pathwaysYoung miceAtherosclerosis-susceptible regionsConclusionThese dataICAM-1VCAM-1NF-κBRelA NF-κB subunitMarker expressionLow levelsFibronectin depositionInflammationMechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels
Batra N, Burra S, Siller-Jackson AJ, Gu S, Xia X, Weber GF, DeSimone D, Bonewald LF, Lafer EM, Sprague E, Schwartz MA, Jiang JX. Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 3359-3364. PMID: 22331870, PMCID: PMC3295295, DOI: 10.1073/pnas.1115967109.Peer-Reviewed Original ResearchMeSH KeywordsAndrostadienesAnimalsCell LineChromonesConnexin 43Extracellular Matrix ProteinsFibronectinsImmunomagnetic SeparationIntegrin alpha5beta1MiceMorpholinesOsteocytesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Interaction MappingRNA, Small InterferingStress, MechanicalWortmannin
2011
JNK2 Promotes Endothelial Cell Alignment under Flow
Hahn C, Wang C, Orr AW, Coon BG, Schwartz MA. JNK2 Promotes Endothelial Cell Alignment under Flow. PLOS ONE 2011, 6: e24338. PMID: 21909388, PMCID: PMC3164210, DOI: 10.1371/journal.pone.0024338.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase c-Jun N-terminal kinaseProtein kinase c-Jun N-terminal kinaseC-Jun N-terminal kinaseActin stress fibersN-terminal kinaseFocal adhesionsBasement membrane proteinsMembrane proteinsLaminar shear stressStress fibersGene expressionJNK activityIntegrin activationJNK2 activationEndothelial cell alignmentJNK activationActivated JNKExtracellular matrixInflammatory gene expressionCell alignmentUnexpected connectionEndothelial cellsActivationPathwayCells
2010
Atheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation
Feaver RE, Gelfand BD, Wang C, Schwartz MA, Blackman BR. Atheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation. Circulation Research 2010, 106: 1703-1711. PMID: 20378855, PMCID: PMC2891748, DOI: 10.1161/circresaha.109.216283.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedDisease Models, AnimalEndothelium, VascularFeedback, PhysiologicalFibronectinsHemodynamicsHumansInflammationMechanotransduction, CellularMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1Pulsatile FlowRegional Blood FlowRNA InterferenceStress, MechanicalTime FactorsTransfectionUp-RegulationConceptsFN depositionAtheroprone flowPECAM-1FN expressionTranscription factor NF-kappaB.Platelet endothelial cell adhesion moleculeNF-kappaB activationNF-kappaB activityAtheroprone hemodynamicsHuman endothelial cellsEndothelial inflammationProinflammatory phenotypeAortic archInduction of fibronectinCarotid arteryCell adhesion moleculeExogenous fibronectinInflammatory signalingFN accumulationNF-kappaBSustained increaseNF-kappaB.Nuclear factorTransient increaseEndothelial cells
2009
The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow
Hahn C, Orr AW, Sanders JM, Jhaveri KA, Schwartz MA. The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow. Circulation Research 2009, 104: 995-1003. PMID: 19286608, PMCID: PMC2702158, DOI: 10.1161/circresaha.108.186486.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EAtherosclerosisBasement MembraneCattleCell Culture TechniquesCells, CulturedCollagenDisease Models, AnimalEndothelial CellsEnzyme ActivationExtracellular MatrixFibronectinsHemorheologyInflammationIntegrinsJNK Mitogen-Activated Protein KinasesMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase KinasesOscillometryP21-Activated KinasesPhosphorylationRegional Blood FlowStress, MechanicalCadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix Organization
Dzamba BJ, Jakab KR, Marsden M, Schwartz MA, DeSimone DW. Cadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix Organization. Developmental Cell 2009, 16: 421-432. PMID: 19289087, PMCID: PMC2682918, DOI: 10.1016/j.devcel.2009.01.008.Peer-Reviewed Original ResearchConceptsCadherin adhesionBlastocoel roofPlanar cell polarity signalingMatrix assemblyCell polarity signalingCell-cell adhesionFN fibril formationFN fibril assemblyPolarity signalingFocal adhesionsActin reorganizationXenopus embryosRegulatory pathwaysMyosin contractilityFibronectin matrixMatrix organizationSpatiotemporal localizationCultured cellsCell surfaceAnalogous roleFibril formationFibril assemblyFibrillar matrixMechanical tensionAssemblyThe Force Is with Us
Schwartz MA. The Force Is with Us. Science 2009, 323: 588-589. PMID: 19179515, DOI: 10.1126/science.1169414.Peer-Reviewed Original Research
2007
Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts
Balasubramanian N, Scott DW, Castle JD, Casanova JE, Schwartz MA. Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts. Nature Cell Biology 2007, 9: 1381-1391. PMID: 18026091, PMCID: PMC2715295, DOI: 10.1038/ncb1657.Peer-Reviewed Original ResearchConceptsPlasma membraneLipid raftsAnchorage-dependent signalingArf6-dependent mannerCaveolin-dependent internalizationSmall GTPase Arf6Microtubule-dependent traffickingIntegrin-mediated adhesionRecycling endosomesGTPase Arf6Membrane raftsDetachment of cellsCell spreadingF-actinRaftsArf6MicrotubulesEndosomesRac1TraffickingMembraneCellsEndocytosisSignalingPathwayMatrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis
Orr AW, Stockton R, Simmers MB, Sanders JM, Sarembock IJ, Blackman BR, Schwartz MA. Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis. Journal Of Cell Biology 2007, 176: 719-727. PMID: 17312022, PMCID: PMC2064028, DOI: 10.1083/jcb.200609008.Peer-Reviewed Original ResearchConceptsP21-activated kinaseP21-activated kinase activationAtherosclerosis-prone regionsCell-cell junctionsBasement membrane proteinsMembrane proteinsPAK phosphorylationActivation of PAKKinase activationPAK activationEndothelial permeabilityFibronectinActivationSubendothelial monocytesVivoKinasePhosphorylationProteinVascular permeabilityAtherogenesisRecruitmentCells
2006
Matrix-specific Suppression of Integrin Activation in Shear Stress Signaling
Orr AW, Ginsberg MH, Shattil SJ, Deckmyn H, Schwartz MA. Matrix-specific Suppression of Integrin Activation in Shear Stress Signaling. Molecular Biology Of The Cell 2006, 17: 4686-4697. PMID: 16928957, PMCID: PMC1635406, DOI: 10.1091/mbc.e06-04-0289.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood VesselsCattleCyclic AMP-Dependent Protein KinasesEndothelial CellsEnzyme ActivationExtracellular MatrixFibroblast Growth Factor 2FibronectinsIntegrin alpha2beta1Integrin alpha5beta1Integrin alphaVbeta3Models, BiologicalPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesProtein Kinase CSignal TransductionStress, MechanicalTalinIntegrating Adhesion, Protrusion, and Contraction during Cell Migration
Schwartz MA, Horwitz AR. Integrating Adhesion, Protrusion, and Contraction during Cell Migration. Cell 2006, 125: 1223-1225. PMID: 16814706, DOI: 10.1016/j.cell.2006.06.015.Peer-Reviewed Original Research