2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Ahangari F, Becker C, Foster DG, Chioccioli M, Nelson M, Beke K, Wang X, Justet A, Adams T, Readhead B, Meador C, Correll K, Lili LN, Roybal HM, Rose KA, Ding S, Barnthaler T, Briones N, DeIuliis G, Schupp JC, Li Q, Omote N, Aschner Y, Sharma L, Kopf KW, Magnusson B, Hicks R, Backmark A, Dela Cruz CS, Rosas I, Cousens LP, Dudley JT, Kaminski N, Downey GP. Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1463-1479. PMID: 35998281, PMCID: PMC9757097, DOI: 10.1164/rccm.202010-3832oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBleomycinFibroblastsFibrosisHumansIdiopathic Pulmonary FibrosisLungMiceProtein Kinase InhibitorsSrc-Family KinasesTransforming Growth Factor betaConceptsIdiopathic pulmonary fibrosisHuman precision-cut lung slicesPrecision-cut lung slicesPulmonary fibrosisNormal human lung fibroblastsEpithelial-mesenchymal transitionHuman lung fibroblastsFibrogenic pathwaysPreclinical modelsMurine modelLung slicesSrc kinase inhibitorLung fibroblastsKinase inhibitorsAmelioration of fibrosisSelective Src kinase inhibitorHuman lung fibrosisWhole lung extractsPotential therapeutic efficacyIPF diseaseIPF treatmentLung functionInflammatory cascadeLung fibrosisAntifibrotic efficacyMicroenvironmental sensing by fibroblasts controls macrophage population size
Zhou X, Franklin RA, Adler M, Carter TS, Condiff E, Adams TS, Pope SD, Philip NH, Meizlish ML, Kaminski N, Medzhitov R. Microenvironmental sensing by fibroblasts controls macrophage population size. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2205360119. PMID: 35930670, PMCID: PMC9371703, DOI: 10.1073/pnas.2205360119.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CountCell ProliferationFibroblastsHippo Signaling PathwayMacrophagesTransforming Growth Factor betaYAP-Signaling ProteinsConceptsCell typesDensity-dependent gene expressionTGF-β target genesDiverse cell typesActin-dependent mechanismLineage-specific growth factorsDistinct cell typesGrowth factor availabilityActivation of YAP1Different cell typesExpression programsMicroenvironmental sensingTranscriptional coactivatorTarget genesGene expressionPopulation sizeFactor availabilityPopulation numbersTissue environmentTissue integrityHippoProliferation of macrophagesYAP1Animal tissuesMechanical forcesPseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis
Brereton CJ, Yao L, Davies ER, Zhou Y, Vukmirovic M, Bell JA, Wang S, Ridley RA, Dean L, Andriotis OG, Conforti F, Brewitz L, Mohammed S, Wallis T, Tavassoli A, Ewing RM, Alzetani A, Marshall BG, Fletcher SV, Thurner PJ, Fabre A, Kaminski N, Richeldi L, Bhaskar A, Schofield CJ, Loxham M, Davies DE, Wang Y, Jones MG. Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis. ELife 2022, 11: e69348. PMID: 35188460, PMCID: PMC8860444, DOI: 10.7554/elife.69348.Peer-Reviewed Original ResearchConceptsHIF pathway activationPathway activationLung fibrosisOxidative stressHuman lung fibrosisOxidative stress scoreFibrillar collagen synthesisHypoxia-inducible factor (HIF) pathway activationExtracellular matrixActive fibrogenesisFibrosisHuman fibrosisFibrosis tissueHIF activationStress scoresVivo studiesCollagen synthesisMesenchymal cellsCritical pathwaysDownstream activationNormal fibroblastsCritical regulatorHIFActivationHuman tissues
2021
Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Chandran RR, Xie Y, Gallardo-Vara E, Adams T, Garcia-Milian R, Kabir I, Sheikh AQ, Kaminski N, Martin KA, Herzog EL, Greif DM. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nature Communications 2021, 12: 7179. PMID: 34893592, PMCID: PMC8664937, DOI: 10.1038/s41467-021-27499-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDisease Models, AnimalDown-RegulationExtracellular MatrixFemaleFibroblastsFibrosisHumansKruppel-Like Factor 4LungLung InjuryMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsReceptor, Platelet-Derived Growth Factor betaRespiratory Tract DiseasesSignal TransductionTransforming Growth Factor betaConceptsMesenchymal cell typesPlatelet-derived growth factor receptorSmooth muscle actinLung fibrosisKruppel-like factor 4Forkhead box M1Growth factor receptorCell transitionCell typesExtracellular matrixDistinct rolesKLF4Box M1C chemokine ligandMesenchymal cell subtypesFactor receptorPro-fibrotic effectsFactor 4PDGFRMesenchymeCellsMacrophage accumulationKLF4 levelsChemokine ligandLung fibrogenesis
2018
An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm
Lino Cardenas CL, Kessinger CW, Cheng Y, MacDonald C, MacGillivray T, Ghoshhajra B, Huleihel L, Nuri S, Yeri AS, Jaffer FA, Kaminski N, Ellinor P, Weintraub NL, Malhotra R, Isselbacher EM, Lindsay ME. An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm. Nature Communications 2018, 9: 1009. PMID: 29520069, PMCID: PMC5843596, DOI: 10.1038/s41467-018-03394-7.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAnimalsAortaAortic Aneurysm, ThoracicCell LineCell NucleusChromatinDisease Models, AnimalDNA HelicasesDNA MethylationFemaleFluorescent Antibody TechniqueHistone DeacetylasesHistonesHumansMaleMiceMice, KnockoutMuscle, Smooth, VascularMutationMyocytes, Smooth MuscleNuclear ProteinsPhenotypePrimary Cell CultureRepressor ProteinsRNA InterferenceRNA, Long NoncodingRNA, Small InterferingSignal TransductionTranscription FactorsTransforming Growth Factor betaConceptsChromatin-remodeling enzyme BRG1Contractile protein gene expressionProtein gene expressionLong noncoding RNA MALAT1Noncoding RNA MALAT1Bind chromatinTGF-β signalingTrimethylation modificationActomyosin cytoskeletonEpigenetic pathwaysContractile protein expressionGene expressionSimilar phenotypeRNA MALAT1Ternary complexBRG1HDAC9VSMC dysfunctionAortic aneurysmCytoskeletonProtein expressionPotential common mechanismsCommon mechanismSmooth muscle dysfunctionMutations
2017
Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases
Bansal R, Nakagawa S, Yazdani S, van Baarlen J, Venkatesh A, Koh AP, Song WM, Goossens N, Watanabe H, Beasley MB, Powell CA, Storm G, Kaminski N, van Goor H, Friedman SL, Hoshida Y, Prakash J. Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases. Experimental & Molecular Medicine 2017, 49: e396-e396. PMID: 29147013, PMCID: PMC5704196, DOI: 10.1038/emm.2017.213.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationDisease Models, AnimalFibrosisGene Expression RegulationGene Knockdown TechniquesHedgehog ProteinsHepatic Stellate CellsHumansImmunohistochemistryIntegrin alpha ChainsKidney DiseasesLiver CirrhosisMiceMyofibroblastsPhenotypeSignal TransductionTransforming Growth Factor betaConceptsHepatic stellate cellsFibrotic parametersMouse modelStellate cellsTissue fibrosisIntegrin alpha 11Alpha 11Smooth muscle actin-positive myofibroblastsLiver fibrosis mouse modelHuman hepatic stellate cellsMyofibroblast phenotypeFibrosis mouse modelPromising therapeutic targetActin-positive myofibroblastsCause of mortalityGrowth factor βAberrant extracellular matrixImpaired contractilityFibrogenic signalingFibrotic organsFibrogenic processExtracellular matrixTherapeutic targetOrgan fibrosisMyofibroblastic differentiation
2014
Wnt Coreceptor Lrp5 Is a Driver of Idiopathic Pulmonary Fibrosis
Lam AP, Herazo-Maya JD, Sennello JA, Flozak AS, Russell S, Mutlu GM, Budinger GR, DasGupta R, Varga J, Kaminski N, Gottardi CJ. Wnt Coreceptor Lrp5 Is a Driver of Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 185-195. PMID: 24921217, PMCID: PMC4226053, DOI: 10.1164/rccm.201401-0079oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsBeta CateninBiomarkersDisease ProgressionFemaleHumansIdiopathic Pulmonary FibrosisLeukocytes, MononuclearLow Density Lipoprotein Receptor-Related Protein-5Low Density Lipoprotein Receptor-Related Protein-6MaleMiceMice, KnockoutMiddle AgedProspective StudiesSeverity of Illness IndexSignal TransductionTransforming Growth Factor betaWnt ProteinsConceptsIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsBlood mononuclear cellsLung fibrosisPulmonary fibrosisDisease progressionMononuclear cellsDisease severityNull miceAlveolar type 2 cellsTGF-β productionWild-type miceActivation of TGFType 2 cellsWnt pathway inhibitorsWnt/β-catenin signalingWnt coreceptors LRP5Role of LRP5Bone marrow cellsLrp5 lossΒ-catenin signalingPatient selectionSmall molecular inhibitorsAdditional cohortFibrosisLet-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts
Huleihel L, Ben-Yehudah A, Milosevic J, Yu G, Pandit K, Sakamoto K, Yousef H, LeJeune M, Coon TA, Redinger CJ, Chensny L, Manor E, Schatten G, Kaminski N. Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2014, 306: l534-l542. PMID: 24441869, PMCID: PMC3949080, DOI: 10.1152/ajplung.00149.2013.Peer-Reviewed Original ResearchMeSH KeywordsActinsCadherinsCalcium-Binding ProteinsCell MovementCell ProliferationCells, CulturedEpithelial-Mesenchymal TransitionFibroblastsFibronectinsHMGA2 ProteinHMGB2 ProteinHumansIdiopathic Pulmonary FibrosisKeratin-19LungMicroRNAsMyofibroblastsPulmonary AlveoliPulmonary FibrosisS100 Calcium-Binding Protein A4Snail Family Transcription FactorsTranscription FactorsTransfectionTransforming Growth Factor betaWound HealingZonula Occludens-1 ProteinConceptsLet-7dFibroblast-specific protein-1Mesenchymal marker αProtein 1Tight junction protein 1Smooth muscle actinMicroRNA Let-7dLung fibrosisProliferation of fibroblastsFibrotic processPrimary fibroblastsEffect of transfectionMuscle actinMesenchymal transitionLung fibroblastsFibroblast responsivenessMesenchymal propertiesKeratin 19Protein expressionEpithelial cellsWound healingN-cadherinProtein inductionReduced motilityTGF
2013
miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1
Cardenas C, Henaoui IS, Courcot E, Roderburg C, Cauffiez C, Aubert S, Copin MC, Wallaert B, Glowacki F, Dewaeles E, Milosevic J, Maurizio J, Tedrow J, Marcet B, Lo-Guidice JM, Kaminski N, Barbry P, Luedde T, Perrais M, Mari B, Pottier N. miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1. PLOS Genetics 2013, 9: e1003291. PMID: 23459460, PMCID: PMC3573122, DOI: 10.1371/journal.pgen.1003291.Peer-Reviewed Original ResearchConceptsIdiopathic formMiR-199aIPF patientsMouse modelUnilateral ureteral obstruction (UUO) mouse modelLung fibroblastsFibrotic lung diseaseLung fibroblast activationBile duct ligationPoor response ratesNew therapeutic strategiesCultured lung fibroblastsDifferent mouse strainsKey cell typesPulmonary expressionHistologic featuresPulmonary fibrosisFibroblastic fociLung diseaseLung fibrosisCurrent therapiesFibrogenic responseKidney fibrosisLiver fibrosisBleomycin exposure
2011
Matrix Metalloproteinase 3 Is a Mediator of Pulmonary Fibrosis
Yamashita CM, Dolgonos L, Zemans RL, Young SK, Robertson J, Briones N, Suzuki T, Campbell MN, Gauldie J, Radisky DC, Riches DW, Yu G, Kaminski N, McCulloch CA, Downey GP. Matrix Metalloproteinase 3 Is a Mediator of Pulmonary Fibrosis. American Journal Of Pathology 2011, 179: 1733-1745. PMID: 21871427, PMCID: PMC3181358, DOI: 10.1016/j.ajpath.2011.06.041.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBeta CateninBleomycinCadherinsCyclin D1Disease Models, AnimalEpithelial CellsEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, EnzymologicGenetic VectorsHumansLungMatrix Metalloproteinase 2Matrix Metalloproteinase 3Matrix Metalloproteinase 9MiceMice, Inbred C57BLProtein TransportPulmonary FibrosisRatsRats, Sprague-DawleyRNA, MessengerSignal TransductionTransforming Growth Factor betaConceptsIdiopathic pulmonary fibrosisMatrix metalloproteinase-3Pathogenesis of IPFPulmonary fibrosisEpithelial-mesenchymal transitionMetalloproteinase-3Recombinant MMP-3Accumulation of myofibroblastsΒ-cateninCultured lung epithelial cellsAberrant repair processProliferation of myofibroblastsAdenoviral vector-mediated expressionMMP-3 expressionLung epithelial cellsCyclin D1 expressionVector-mediated expressionQuantitative RT-PCRWestern blot analysisΒ-catenin signalingEpithelial injuryLung architectureVitro treatmentRat lungFibrosis
2010
Inhibition and Role of let-7d in Idiopathic Pulmonary Fibrosis
Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF, Konishi K, Yousem SA, Singh M, Handley D, Richards T, Selman M, Watkins SC, Pardo A, Ben-Yehudah A, Bouros D, Eickelberg O, Ray P, Benos PV, Kaminski N. Inhibition and Role of let-7d in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2010, 182: 220-229. PMID: 20395557, PMCID: PMC2913236, DOI: 10.1164/rccm.200911-1698oc.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCadherinsCells, CulturedDown-RegulationEpithelial CellsHMGA2 ProteinHumansIdiopathic Pulmonary FibrosisIn Situ HybridizationLungMiceMice, Inbred C57BLMicroRNAsPolymerase Chain ReactionPulmonary AlveoliS100 Calcium-Binding Protein A4S100 ProteinsSmad3 ProteinTransforming Growth Factor betaVimentinConceptsIdiopathic pulmonary fibrosisReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionAlveolar epithelial cellsIPF lungsPulmonary fibrosisPolymerase chain reactionLet-7dEpithelial cellsLethal fibrotic lung diseaseAlpha-smooth muscle actinAlveolar septal thickeningMesenchymal markers N-cadherinFibrotic lung diseaseChain reactionLet-7d expressionSeptal thickeningPulmonary functionLung diseaseLung fibrosisEpithelial cell lineIntratracheal administrationIPF tissueProfibrotic effectsClinical trials
2009
Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury
Scotton CJ, Krupiczojc MA, Königshoff M, Mercer PF, Lee YC, Kaminski N, Morser J, Post JM, Maher TM, Nicholson AG, Moffatt JD, Laurent GJ, Derian CK, Eickelberg O, Chambers RC. Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. Journal Of Clinical Investigation 2009, 119: 2550-2563. PMID: 19652365, PMCID: PMC2735922, DOI: 10.1172/jci33288.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdultAgedAnimalsBase SequenceBleomycinCase-Control StudiesCell DifferentiationCells, CulturedFactor XaFactor Xa InhibitorsFemaleFibroblastsGene ExpressionHumansIdiopathic Pulmonary FibrosisLung InjuryMaleMiceMice, Inbred C57BLMiddle AgedModels, BiologicalPulmonary FibrosisReceptor, PAR-1Receptors, VitronectinRNA, MessengerTransforming Growth Factor betaUp-RegulationConceptsProteinase-activated receptor 1Lung injuryPulmonary fibrosisFibrotic responseCoagulation cascade contributesExcessive procoagulant activityChronic lung diseaseIdiopathic pulmonary fibrosisMurine lung injuryDirect FXa inhibitorsFibrotic lung tissueHuman adult lungFactor XTGF-beta activationNovel pathogenetic mechanismLung biopsyMicrovascular leakFibrotic fociLung diseaseFibrosis developmentLung tissuePathogenetic mechanismsAlpha-SMATissue injuryAlveolar epithelium
2008
Cross Talk between Id1 and Its Interactive Protein Dril1 Mediate Fibroblast Responses to Transforming Growth Factor-β in Pulmonary Fibrosis
Lin L, Zhou Z, Zheng L, Alber S, Watkins S, Ray P, Kaminski N, Zhang Y, Morse D. Cross Talk between Id1 and Its Interactive Protein Dril1 Mediate Fibroblast Responses to Transforming Growth Factor-β in Pulmonary Fibrosis. American Journal Of Pathology 2008, 173: 337-346. PMID: 18583319, PMCID: PMC2475772, DOI: 10.2353/ajpath.2008.070915.Peer-Reviewed Original ResearchConceptsLung fibrosisPulmonary fibrosisGrowth factorSuppression of fibrosisTranscriptional regulator inhibitorIdiopathic pulmonary fibrosisProgressive lung fibrosisEffects of Id1Activation of TGFInhibited DNA bindingProfibrotic functionsDisease progressionFibrosisFibrotic diseasesDifferentiation 1TGFPotential mechanismsId1FibroblastsNovel binding partnerHuman fibroblastsDRIL1Target genesPatientsLungTransgelin is a direct target of TGF‐β/Smad3‐dependent epithelial cell migration in lung fibrosis
Yu H, Königshoff M, Jayachandran A, Handley D, Seeger W, Kaminski N, Eickelberg O. Transgelin is a direct target of TGF‐β/Smad3‐dependent epithelial cell migration in lung fibrosis. The FASEB Journal 2008, 22: 1778-1789. PMID: 18245174, DOI: 10.1096/fj.07-083857.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisReverse transcription-polymerase chain reactionLung fibrosisATII cellsPulmonary fibrosisType II cell hyperplasiaExcessive extracellular matrix depositionATII cell phenotypeCell phenotypeTranscription-polymerase chain reactionLung epithelial A549 cellsPrimary ATII cellsActivin-like kinase 5Epithelial A549 cellsTGF-beta treatmentExtracellular matrix depositionTransgelin geneIPF patientsTGF-beta signalingCell hyperplasiaTGF-beta target genesCell injuryLung specimenFibrosisFatal disease
2003
Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema
Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD, Dolganov G, Glick A, Sheppard D. Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema. Nature 2003, 422: 169-173. PMID: 12634787, DOI: 10.1038/nature01413.Peer-Reviewed Original ResearchConceptsTGF-β activationLungs of miceActive TGF-β1Pulmonary gene expressionHeterodimeric cell-surface proteinsTransgenic expressionPulmonary emphysemaMMP12 expressionTGF-β1Functional alterationsΒ6 integrinIntegrin αvβ6Latent TGFMarked inductionEmphysemaGrowth factorMacrophage metalloelastaseCell surface proteinsActivation pathwayMiceTGFActivationCell growthIntegrinsExpressionGlobal Expression Profiling of Fibroblast Responses to Transforming Growth Factor-β1 Reveals the Induction of Inhibitor of Differentiation-1 and Provides Evidence of Smooth Muscle Cell Phenotypic Switching
Chambers RC, Leoni P, Kaminski N, Laurent GJ, Heller RA. Global Expression Profiling of Fibroblast Responses to Transforming Growth Factor-β1 Reveals the Induction of Inhibitor of Differentiation-1 and Provides Evidence of Smooth Muscle Cell Phenotypic Switching. American Journal Of Pathology 2003, 162: 533-546. PMID: 12547711, PMCID: PMC1851161, DOI: 10.1016/s0002-9440(10)63847-3.Peer-Reviewed Original ResearchMeSH KeywordsCell DivisionCell LineCell SurvivalFetusFibroblastsGene Expression ProfilingHelix-Loop-Helix MotifsHumansImmunohistochemistryInhibitor of Differentiation Protein 1Inhibitor of Differentiation ProteinsLungMuscle, SmoothNeoplasm ProteinsPhenotypeRepressor ProteinsRNA, MessengerTranscription FactorsTranscription, GeneticTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsMajor functional categoriesHelix transcription factorGlobal gene expressionNumber of genesCell lineage commitmentGlobal expression profilingDominant-negative antagonistSmooth muscle cell phenotypic switchingProtein levelsSmooth muscle myosin heavy chainInduction of inhibitorMuscle myosin heavy chainTransformation of fibroblastsImmediate early genesTranscriptional regulatorsTranscriptional programsExtracellular matrix protein depositionTranscriptional programmingProtein biosynthesisGene groupsLineage commitmentCytoskeletal reorganizationTranscription factorsFunctional categoriesCell signaling
2001
TGF-β is a critical mediator of acute lung injury
Pittet J, Griffiths M, Geiser T, Kaminski N, Dalton S, Huang X, Brown L, Gotwals P, Koteliansky V, Matthay M, Sheppard D. TGF-β is a critical mediator of acute lung injury. Journal Of Clinical Investigation 2001, 107: 1537-1544. PMID: 11413161, PMCID: PMC200192, DOI: 10.1172/jci11963.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, NeoplasmBleomycinBlood-Air BarrierCells, CulturedEndotoxinsGlutathioneIntegrinsMiceMice, KnockoutProtein Serine-Threonine KinasesPulmonary AlveoliPulmonary EdemaReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaRespiratory Distress SyndromeTransforming Growth Factor betaConceptsAcute lung injuryPulmonary edemaLung injuryAlveolar epithelial permeabilityWild-type miceEscherichia coli endotoxinColi endotoxinEffective treatmentEpithelial permeabilityIntegrin alphavbeta6Pharmacologic inhibitionEdemaCritical mediatorUntreatable disorderLocal activationIntracellular glutathioneInjuryMiceActivationLungTGFBleomycinEndotoxin
1999
A Mechanism for Regulating Pulmonary Inflammation and Fibrosis: The Integrin αvβ6 Binds and Activates Latent TGF β1
Munger J, Huang X, Kawakatsu H, Griffiths M, Dalton S, Wu J, Pittet J, Kaminski N, Garat C, Matthay M, Rifkin D, Sheppard D. A Mechanism for Regulating Pulmonary Inflammation and Fibrosis: The Integrin αvβ6 Binds and Activates Latent TGF β1. Cell 1999, 96: 319-328. PMID: 10025398, DOI: 10.1016/s0092-8674(00)80545-0.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsAntigens, NeoplasmBleomycinCHO CellsCricetinaeEpithelial CellsEsophagusHumansIntegrinsKeratinocytesLigandsMiceMice, KnockoutPeptide FragmentsProtein BindingProtein PrecursorsProteinsPulmonary FibrosisTransforming Growth Factor betaTransforming Growth Factor beta1Tumor Cells, CulturedConceptsLatency-associated peptideIntegrin alpha v beta 6Alpha v beta 6 integrinAlpha v beta 6Beta gene productsTGF beta 1Latent TGF-β1TGF-beta functionGrowth factor-beta (TGF-beta) family membersPulmonary inflammationExaggerated inflammationPulmonary fibrosisTGF-β1Beta 6Alpha vBeta 1Beta family membersInflammationFibrosisFamily membersNovel mechanismExtracellular activationVivoActivationIntegrins