2025
A genetic modifier links integrin α5 to the phenotypic variation in fibronectin 1a mutant zebrafish.
Capon S, Maroufidou A, Feltes M, Xu Y, Matharoo D, Jülich D, Holley S, Farber S, Stainier D. A genetic modifier links integrin α5 to the phenotypic variation in fibronectin 1a mutant zebrafish. PLOS Genetics 2025, 21: e1011747. PMID: 40549824, PMCID: PMC12212883, DOI: 10.1371/journal.pgen.1011747.Peer-Reviewed Original ResearchConceptsMutant phenotypePhenotypic variationNonsense mutationGenetic modifiersDouble mutant analysisWhole-genome sequencingITGA5 expressionSevere phenotypeIntegrin alpha 5Mutant analysisMutant larvaeProximal promoterMutantsMutant zebrafishCardia bifidaGene expressionIntegrin A5Genetic backgroundAlpha 5PhenotypeMutationsExpression levelsFibronectinFunctional cardiovascular systemZebrafishFibronectin matrix assembly at a glance.
Sun Y, Hamlin A, Schwarzbauer J. Fibronectin matrix assembly at a glance. Journal Of Cell Science 2025, 138 PMID: 40130407, PMCID: PMC12050093, DOI: 10.1242/jcs.263834.Peer-Reviewed Original ResearchConceptsAbundant ECM proteinFibronectin matrix assemblyOrganization of FNExtracellular matrixMechanisms of extracellular matrixSecrete ECM componentsFN assemblyDomain organizationFN fibrilsFN matrixGlance articleECM proteinsMatrix assemblyECM componentsIntracellular pathwaysFibrillar matrixReceptor-mediated processFibronectinCell scienceProteinAssemblyCellsCell-mediated processPathwayMechanismDSP-1, the major fibronectin type-II protein of donkey seminal plasma is a small heat-shock protein and exhibits chaperone-like activity against thermal and oxidative stress
Alim S, Cheppali S, Pawar S, Swamy M. DSP-1, the major fibronectin type-II protein of donkey seminal plasma is a small heat-shock protein and exhibits chaperone-like activity against thermal and oxidative stress. Biochimica Et Biophysica Acta (BBA) - Proteins And Proteomics 2025, 1873: 141064. PMID: 39956303, DOI: 10.1016/j.bbapap.2025.141064.Peer-Reviewed Original ResearchConceptsChaperone-like activitySeminal plasmaFibronectin type IITetramer to monomersSperm capacitationSurface hydrophobicityMolecular chaperonesClient proteinsHeat shock proteinsBiophysical studiesAlcohol dehydrogenaseOxidative stressPhysiological ligandsShock proteinsProteinHead group moietySHspsBinding of phosphorylcholineCholine phospholipidsBindingFibronectinDehydrogenaseChaperoneSpermMammalsAn Injectable Alginate Hydrogel Modified by Collagen and Fibronectin for Better Cellular Environment
Gao D, Shipman W, Sun Y, Yang W, Mathew A, Beraki L, Glahn J, Kochen A, Kyriakides T, Horsley V, Hsia H. An Injectable Alginate Hydrogel Modified by Collagen and Fibronectin for Better Cellular Environment. ACS Applied Bio Materials 2025, 8: 1675-1683. PMID: 39886738, DOI: 10.1021/acsabm.4c01853.Peer-Reviewed Original ResearchConceptsEncapsulated fibroblastsAlginate hydrogelNeat alginate hydrogelsComposite hydrogelsModified hydrogelsInjectable hydrogelsStorage modulusMechanical propertiesCollagen hydrogelsMacroporous structureHydrogelsPore sizeAlginate functionalizationAlginate controlAlginate matrixAlginateFibroblast behaviorPro-angiogenic potentialFibroblast spreadingModulusPromote wound healingPoreFormation of fibrils
2024
Identification of a fibronectin-binding protein signature associated with idiopathic pulmonary fibrosis
Sun Y, King B, Hamlin A, Saniepay M, Gorshkov K, Barker G, Ziegler M, Mukundan S, Cvijic M, Schwarzbauer J. Identification of a fibronectin-binding protein signature associated with idiopathic pulmonary fibrosis. Cells And Development 2024, 179: 203941. PMID: 39038657, PMCID: PMC11344656, DOI: 10.1016/j.cdev.2024.203941.Peer-Reviewed Original ResearchConceptsFn-binding proteinsExtracellular matrixInsulin-like growth factor binding protein-3Extracellular matrix protein fibronectinLevels of ECM proteinsExtracellular matrix proteinsIn vivo diseaseMatrisome genesEDB exonsProtein fibronectinECM proteinsRNA sequencingGene expressionTGF-bDown-regulationProteinHuman lung fibroblastsUp-regulatedLevels of FNProtein signaturesFibronectinFN expressionGrowth factor binding protein-3ExonAssociated with idiopathic pulmonary fibrosisRare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer’s disease
Bhattarai P, Gunasekaran T, Belloy M, Reyes-Dumeyer D, Jülich D, Tayran H, Yilmaz E, Flaherty D, Turgutalp B, Sukumar G, Alba C, McGrath E, Hupalo D, Bacikova D, Le Guen Y, Lantigua R, Medrano M, Rivera D, Recio P, Nuriel T, Ertekin-Taner N, Teich A, Dickson D, Holley S, Greicius M, Dalgard C, Zody M, Mayeux R, Kizil C, Vardarajan B. Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer’s disease. Acta Neuropathologica 2024, 147: 70. PMID: 38598053, PMCID: PMC11006751, DOI: 10.1007/s00401-024-02721-1.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlzheimer DiseaseAnimalsChild, PreschoolFibronectinsGenetic VariationGliosisHumansZebrafishConceptsLoss-of-functionWhole-genome sequencingFibronectin 1Genetic variationAlzheimer's diseaseAD riskRare coding variantsLoss-of-function variantsRare genetic variationGene Ontology termsFamily based studyIn vivo functional studiesAD-related pathologyAlpha 2 chainOntology termsPresence of cellular mechanismsProtective variantsECM proteinsAD pathologyPathway analysisFunctional studiesUnaffected carriersZebrafish modelAPOEe4 alleleProtein levels
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/Downregulation of a tumor suppressor gene LKB1 in lung transplantation as a biomarker for chronic murine lung allograft rejection
Rahman M, Ravichandran R, Sankpal N, Bansal S, Sureshbabu A, Fleming T, Perincheri S, Bharat A, Smith M, Bremner R, Mohanakumar T. Downregulation of a tumor suppressor gene LKB1 in lung transplantation as a biomarker for chronic murine lung allograft rejection. Cellular Immunology 2023, 386: 104690. PMID: 36812767, PMCID: PMC11019891, DOI: 10.1016/j.cellimm.2023.104690.Peer-Reviewed Original ResearchConceptsLung allograft rejectionLung transplantationAllograft rejectionChronic lung allograft rejectionBronchiolitis obliterans syndromeLung transplant recipientsTumor suppressor gene LKB1Phosphorylated mammalian targetBEAS-2B cellsObliterans syndromeChronic rejectionTransplant recipientsDonor lungsSingle lungB6D2F1 miceMurine modelDBA/2J miceMTOR expressionMammalian targetLKB1 overexpressionSignificant downregulationLungLKB1 knockdownA549 cellsLKB1 activity
2022
Fibroblasts secrete fibronectin under lamellipodia in a microtubule- and myosin II–dependent fashion
Huet-Calderwood C, Rivera-Molina F, Toomre D, Calderwood D. Fibroblasts secrete fibronectin under lamellipodia in a microtubule- and myosin II–dependent fashion. Journal Of Cell Biology 2022, 222: e202204100. PMID: 36416725, PMCID: PMC9699186, DOI: 10.1083/jcb.202204100.Peer-Reviewed Original ResearchConceptsFN secretionFocal adhesion dynamicsExtracellular matrixFocal adhesion formationSites of exocytosisLive-cell microscopyIntegrin-independent mannerCytoskeletal dynamicsFocal adhesionsAdhesion dynamicsRegulatory componentsMyosin IIIntact microtubulesCell polarizationCell adhesionIntegrin receptorsFN depositionLamellipodiaMicrotubulesFibronectinAdhesion formationNew adhesion formationFibroblastsII-dependent fashionCellsFibronectin-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 membraneT1DFurther delineation of familial polycystic ovary syndrome (PCOS) via whole‐exome sequencing: PCOS‐related rare FBN3 and FN1 gene variants are identified
Karakaya C, Çil AP, Bilguvar K, Çakir T, Karalok MH, Karabacak RO, Caglayan AO. Further delineation of familial polycystic ovary syndrome (PCOS) via whole‐exome sequencing: PCOS‐related rare FBN3 and FN1 gene variants are identified. Journal Of Obstetrics And Gynaecology Research 2022, 48: 1202-1211. PMID: 35141985, PMCID: PMC9050819, DOI: 10.1111/jog.15187.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeWhole-exome sequencingFurther functional studiesMissense variantsNew drug targetsGerm-line DNAWhole-exome sequencing dataThree-dimensional structurePolycystic ovary syndrome patientsFunctional predictionChemogenomic analysisCandidate proteinsSequencing dataBiological pathwaysDrug targetsFunctional studiesCandidate variantsSequencingPCOS familiesRotterdam criteriaOvary syndromeFBN3Syndrome patientsPathwayPCOS probands
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
2020
Cell-Extracellular Matrix Interactions Play Multiple Essential Roles in Aortic Arch Development
Warkala M, Chen D, Ramirez A, Jubran A, Schonning M, Wang X, Zhao H, Astrof S. Cell-Extracellular Matrix Interactions Play Multiple Essential Roles in Aortic Arch Development. Circulation Research 2020, 128: e27-e44. PMID: 33249995, PMCID: PMC7864893, DOI: 10.1161/circresaha.120.318200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicCell LineageCell-Matrix JunctionsEndothelial Progenitor CellsExtracellular MatrixExtracellular Matrix ProteinsFibronectinsGene Expression Regulation, DevelopmentalGestational AgeIntegrin alpha5beta1LIM-Homeodomain ProteinsMice, 129 StrainMice, Inbred C57BLMice, KnockoutMorphogenesisSignal TransductionTranscription FactorsConceptsSecond heart fieldPharyngeal arch arteriesCell-ECM interactionsPAA formationAortic arch arteriesPharyngeal archesArch arteriesIntegrin α5β1Whole-mount confocal imagingEssential roleCell-extracellular matrix interactionsFourth pharyngeal arch arteryMultiple essential rolesEndothelial cell dynamicsNeural crest-derived cellsCrest-derived cellsLethal birth defectEC progenitorsUnderstanding genesHeart fieldLineage tracingVascular smooth muscle cellsMorphogenesisAortic arch developmentDevelopmental stagesTGFβ (Transforming Growth Factor-Beta)–Activated Kinase 1 Regulates Arteriovenous Fistula Maturation
Hu H, Lee SR, Bai H, Guo J, Hashimoto T, Isaji T, Guo X, Wang T, Wolf K, Liu S, Ono S, Yatsula B, Dardik A. TGFβ (Transforming Growth Factor-Beta)–Activated Kinase 1 Regulates Arteriovenous Fistula Maturation. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: e203-e213. PMID: 32460580, PMCID: PMC7316601, DOI: 10.1161/atvbaha.119.313848.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaArteriovenous Shunt, SurgicalCells, CulturedCollagen Type IEndothelial CellsFibronectinsHumansJNK Mitogen-Activated Protein KinasesMaleMAP Kinase Kinase KinasesMechanotransduction, CellularMice, Inbred C57BLp38 Mitogen-Activated Protein KinasesPhosphorylationStress, MechanicalVascular PatencyVascular RemodelingVena Cava, InferiorConceptsArteriovenous fistulaAVF maturationNoncanonical TGFβSuccessful AVF maturationArteriovenous fistula maturationNovel therapeutic approachesTAK1 functionsFistula maturationHemodialysis accessDeposition of ECMLuminal diameterMouse endothelial cellsMaturation failureTherapeutic approachesLumen dilationControl veinsWall thickeningAVF modelOptimal conduitArterial magnitudesEndothelial cellsTAK1 phosphorylationCollagen 1Growth factorLaminar shear stressFibronectin is a smart adhesive that both influences and responds to the mechanics of early spinal column development
Guillon E, Das D, Jülich D, Hassan AR, Geller H, Holley S. Fibronectin is a smart adhesive that both influences and responds to the mechanics of early spinal column development. ELife 2020, 9: e48964. PMID: 32228864, PMCID: PMC7108867, DOI: 10.7554/elife.48964.Peer-Reviewed Original ResearchMeSH KeywordsAdhesivesAnimalsExtracellular MatrixFemaleFibronectinsHumansMaleMesodermMorphogenesisNeural TubeSpineZebrafishConceptsNeural tubeParaxial mesodermZebrafish neural tubeNormal vertebrate developmentVertebrate trunkVertebrate developmentFibronectin remodelingFibronectin matrixConvergence defectsMorphogenesisExtracellular matrixMesodermFibronectinColumn developmentSmart adhesivesCadherinMutantsAdhesive lap jointsAdhesionLap jointsSymmetric interfacesRemodelingShear stressDefects
2019
Transforming growth factor-β promotes basement membrane fibrosis, alters perivascular cerebrospinal fluid distribution, and worsens neurological recovery in the aged brain after stroke
Howe MD, Furr JW, Munshi Y, Roy-O’Reilly M, Maniskas ME, Koellhoffer EC, d’Aigle J, Sansing LH, McCullough LD, Urayama A. Transforming growth factor-β promotes basement membrane fibrosis, alters perivascular cerebrospinal fluid distribution, and worsens neurological recovery in the aged brain after stroke. GeroScience 2019, 41: 543-559. PMID: 31721012, PMCID: PMC6885082, DOI: 10.1007/s11357-019-00118-7.Peer-Reviewed Original ResearchConceptsPoor functional recoveryFunctional recoveryExperimental strokeAstrocyte activationStroke patientsAged brainCultured astrocytesSerum TGF-β levelsTGF-β receptor inhibitionPotential new treatment strategyGlial scar developmentElderly stroke patientsTGF-β levelsPoor functional outcomeOxygen-glucose deprivationCerebrospinal fluid distributionNew treatment strategiesPrimary cultured astrocytesExogenous TGF-β stimulationBasement membraneTGF-β stimulationNeurological recoveryElderly patientsSerum levelsFunctional outcomeThe role of fatty acid binding protein 7 in spinal cord astrocytes in a mouse model of experimental autoimmune encephalomyelitis
Kamizato K, Sato S, Shil SK, Umaru BA, Kagawa Y, Yamamoto Y, Ogata M, Yasumoto Y, Okuyama Y, Ishii N, Owada Y, Miyazaki H. The role of fatty acid binding protein 7 in spinal cord astrocytes in a mouse model of experimental autoimmune encephalomyelitis. Neuroscience 2019, 409: 120-129. PMID: 31051217, DOI: 10.1016/j.neuroscience.2019.03.050.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisSpinal cordAutoimmune encephalomyelitisMultiple sclerosisWT miceMouse modelFabp7 KO miceSpinal cord astrocytesLumbar spinal cordInduction of inflammationWild-type miceCentral nervous systemProtein 7Role of FABP7Fatty acid homeostasisMRNA expression levelsLate phaseEAE onsetEAE symptomsAstrocyte activationClinical scoresFatty acidsInflammatory cytokinesMyelin degenerationType mice
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 ligandsHMenaExtracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECs
Chen M, Qiu T, Wu J, Yang Y, Wright GD, Wu M, Ge R. Extracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECs. Cell Death & Differentiation 2018, 25: 1905-1920. PMID: 29523874, PMCID: PMC6219483, DOI: 10.1038/s41418-018-0092-9.Peer-Reviewed Original ResearchMeSH KeywordsAngiostatinsApoptosisCell MembraneEndocytosisEndoplasmic Reticulum Chaperone BiPEndosomesFibronectinsFluorescence Recovery After PhotobleachingHeat-Shock ProteinsHuman Umbilical Vein Endothelial CellsHumansMicroscopy, FluorescenceMitochondriaNeovascularization, PhysiologicPhosphoproteinsProtein TransportRecombinant ProteinsRNA InterferenceRNA, Small InterferingSodium-Hydrogen ExchangersSynaptosomal-Associated Protein 25ThrombospondinsConceptsLate endosomesEndosomal proteinExtracellular proteinsT-SNARE proteinsCytosolic scaffold proteinsTotal internal reflection fluorescent microscopyPro-apoptotic functionFluorescent microscopyRegulatory factor 1Recycling endosomesRNAi knockdownCargo degradationScaffold proteinSuper-resolution fluorescent microscopyMitochondrial traffickingCell fractionationPlasma membraneIsthminProximity ligationMitochondriaProtein 25ProteinBiochemical analysisAnti-angiogenic proteinFactor 1Inhibiting 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
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