Featured Publications
Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function
Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo e Drigo R, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nature Medicine 2017, 24: 39-49. PMID: 29200204, PMCID: PMC5760280, DOI: 10.1038/nm.4447.Peer-Reviewed Original Research
2021
PINK1 mediates the protective effects of thyroid hormone T3 in hyperoxia-induced lung injury
Zhang Y, Yu G, Kaminski N, Lee P. PINK1 mediates the protective effects of thyroid hormone T3 in hyperoxia-induced lung injury. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2021, 320: l1118-l1125. PMID: 33851544, PMCID: PMC8285622, DOI: 10.1152/ajplung.00598.2020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHyperoxiaInflammationLungLung InjuryMice, KnockoutMitochondriaProtein KinasesTriiodothyronineConceptsLung injuryWT miceThyroid hormonesBronchoalveolar lavageHyperoxia exposureBAL total cell countT3 pretreatmentAdult wild-type miceAdministration of PTULung cellular infiltratesAcute lung injuryWild-type miceNovel protective roleRespiratory failureCellular infiltrateThyroid hormone T3Total cell countHistological changesProtective effectPotential therapyProtective roleCell countCytoprotective effectsMitochondrial injuryHyperoxia
2020
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition
2019
Transcriptional regulatory model of fibrosis progression in the human lung
McDonough JE, Ahangari F, Li Q, Jain S, Verleden SE, Herazo-Maya J, Vukmirovic M, DeIuliis G, Tzouvelekis A, Tanabe N, Chu F, Yan X, Verschakelen J, Homer RJ, Manatakis DV, Zhang J, Ding J, Maes K, De Sadeleer L, Vos R, Neyrinck A, Benos PV, Bar-Joseph Z, Tantin D, Hogg JC, Vanaudenaerde BM, Wuyts WA, Kaminski N. Transcriptional regulatory model of fibrosis progression in the human lung. JCI Insight 2019, 4 PMID: 31600171, PMCID: PMC6948862, DOI: 10.1172/jci.insight.131597.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAdvanced fibrosisAlveolar surface densityFibrosis progressionLung fibrosisHuman lungDynamic Regulatory Events MinerExtent of fibrosisIPF lungsPulmonary fibrosisControl lungsIPF tissueB lymphocytesFibrosisLungLinear mixed-effects modelsMixed-effects modelsGene expression changesSystems biology modelsDifferential gene expression analysisGene expression analysisProgressionGene expression networksRNA sequencingBiology modelsRole of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosis
Xylourgidis N, Min K, Ahangari F, Yu G, Herazo-Maya JD, Karampitsakos T, Aidinis V, Binzenhöfer L, Bouros D, Bennett AM, Kaminski N, Tzouvelekis A. Role of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2019, 317: l678-l689. PMID: 31483681, PMCID: PMC6879900, DOI: 10.1152/ajplung.00264.2018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticBleomycinDual-Specificity PhosphatasesFemaleFibroblastsHumansMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesPhosphorylationPulmonary FibrosisSignal TransductionTransforming Growth Factor beta1ConceptsPulmonary fibrosisLung fibrosisFibrogenic genesLung fibroblastsM1 macrophage phenotypeIdiopathic pulmonary fibrosisHuman lung fibrosisGrowth factor-β1Levels of hydroxyprolineProtein kinase phosphatase 5IPF lungsReduced fibrosisMuscle fibrosisProfibrogenic effectsTGF-β1Smad7 levelsTherapeutic targetAnimal modelsFactor-β1FibrosisSmad3 phosphorylationEnhanced p38 MAPK activityP38 MAPK activityMyofibroblast differentiationMKP-5 expression
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
Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis
Korde A, Jin L, Zhang JG, Ramaswamy A, Hu B, Kolahian S, Guardela BJ, Herazo-Maya J, Siegfried JM, Stabile L, Pisani MA, Herbst RS, Kaminski N, Elias JA, Puchalski JT, Takyar SS. Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1443-1455. PMID: 28853613, PMCID: PMC5736970, DOI: 10.1164/rccm.201610-2157oc.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerMiR-1 levelsLewis lung carcinoma xenograftsLung carcinoma xenograftsTransgenic miceEndothelial cellsNSCLC tumorsCarcinoma xenograftsLung endotheliumMiR-1Tumor growthTumor progressionVascular endothelial cadherin promoterMicroRNA-1Cohort of patientsTumor-bearing lungsCell lung cancerVascular endothelial growth factorCancer-free tissuesEndothelial growth factorInducible transgenic miceMiR-1 overexpressionKP miceOverall survivalTumor burdenLoss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12
Tan J, Tedrow JR, Nouraie M, Dutta JA, Miller DT, Li X, Yu S, Chu Y, Juan-Guardela B, Kaminski N, Ramani K, Biswas PS, Zhang Y, Kass DJ. Loss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12. The Journal Of Immunology 2017, 198: 2269-2285. PMID: 28179498, PMCID: PMC5337810, DOI: 10.4049/jimmunol.1600610.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIPF patientsLung injuryPulmonary fibrosisT cellsFibrotic lung injuryIPF lung fibroblastsExperimental lung injuryT-cell pathwayApoptosis-resistant fibroblastsMatrix-producing cellsChemoattractant CXCL12Exaggerated fibrosisIPF phenotypeCollagen-producing cellsTranscription factor Twist1Prosurvival phenotypeFibrosisTwist1 expressionIncreased expressionLung fibroblastsCXCL12Low expressionHigh expressionCell pathways
2016
Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis
Peng X, Moore M, Mathur A, Zhou Y, Sun H, Gan Y, Herazo‐Maya J, Kaminski N, Hu X, Pan H, Ryu C, Osafo‐Addo A, Homer RJ, Feghali‐Bostwick C, Fares W, Gulati M, Hu B, Lee C, Elias JA, Herzog EL. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis. The FASEB Journal 2016, 30: 4056-4070. PMID: 27609773, PMCID: PMC5102121, DOI: 10.1096/fj.201600373r.Peer-Reviewed Original ResearchConceptsLung fibrosisPlexin C1Macrophage migrationPulmonary fibrosisBone marrow-derived cellsSynaptotagmin-7Idiopathic pulmonary fibrosisInterstitial lung diseaseMarrow-derived cellsTGF-β1 overexpressionFatal conditionLung diseaseMonocyte migrationUnrecognized observationCollagen accumulationFibrosisMice showBoyden chamberGenetic deletionLungMouse macrophagesSemaphorin receptorsMacrophagesC1s deficiencyDeficiency
2015
Matrix metalloproteinase (MMP)-19-deficient fibroblasts display a profibrotic phenotype
Jara P, Calyeca J, Romero Y, Plácido L, Yu G, Kaminski N, Maldonado V, Cisneros J, Selman M, Pardo A. Matrix metalloproteinase (MMP)-19-deficient fibroblasts display a profibrotic phenotype. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2015, 308: l511-l522. PMID: 25575513, PMCID: PMC5243210, DOI: 10.1152/ajplung.00043.2014.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisBleomycin-induced lung fibrosisLung fibroblastsLethal interstitial lung diseaseInterstitial lung diseaseExcessive extracellular matrix productionWild-type miceMatrix metalloproteinase-19Activation of fibroblastsCollagen protein productionMyofibroblastic fociPulmonary fibrosisLung fibrosisLung diseaseProfibrotic pathwaysUnknown etiologyFibroblast gene expressionDeficient miceProfibrotic phenotypeSmooth muscleMatrix metalloproteinaseMetalloproteinase 19Boyden chamberAbnormal lungMMP-19
2014
Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice
Ganguly K, Martin TM, Concel VJ, Upadhyay S, Bein K, Brant KA, George L, Mitra A, Thimraj TA, Fabisiak JP, Vuga LJ, Fattman C, Kaminski N, Schulz H, Leikauf GD. Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice. American Journal Of Respiratory Cell And Molecular Biology 2014, 51: 637-651. PMID: 24816281, PMCID: PMC4224082, DOI: 10.1165/rcmb.2013-0471oc.Peer-Reviewed Original ResearchMeSH KeywordsAlveolar Epithelial CellsAnimalsAnimals, NewbornCore Binding Factor Alpha 1 SubunitFemaleGene Expression Regulation, DevelopmentalLung ComplianceMaleMice, Inbred C3HMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisOsteopontinPromoter Regions, GeneticPulmonary AlveoliPulmonary Disease, Chronic ObstructiveReceptor, Notch1ConceptsMicroarray analysisPhosphoprotein 1Quantitative trait lociLung functionQuantitative RT-PCR analysisDNA-protein bindingRunt-related transcription factor 2Transcription factor 2Developmental transcriptsLung developmentTrait lociNumerous genesSecreted Phosphoprotein 1Notch1 transcriptsRT-PCR analysisInsulin-like growth factor-1C3H/HeJ miceDiminished lung functionLung function developmentSPP1 promoterSPP1Growth factor-1Mean airspace chord lengthC3H/HeJGenetic variantsWnt 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 cohortFibrosis
2012
Matrix Metalloproteinase-19 Is a Key Regulator of Lung Fibrosis in Mice and Humans
Yu G, Kovkarova-Naumovski E, Jara P, Parwani A, Kass D, Ruiz V, Lopez-Otín C, Rosas IO, Gibson KF, Cabrera S, Ramírez R, Yousem SA, Richards TJ, Chensny LJ, Selman M, Kaminski N, Pardo A. Matrix Metalloproteinase-19 Is a Key Regulator of Lung Fibrosis in Mice and Humans. American Journal Of Respiratory And Critical Care Medicine 2012, 186: 752-762. PMID: 22859522, PMCID: PMC5450991, DOI: 10.1164/rccm.201202-0302oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBleomycinCells, CulturedCyclooxygenase 2Epithelial CellsGene Expression Regulation, EnzymologicHumansIdiopathic Pulmonary FibrosisLaser Capture MicrodissectionMatrix Metalloproteinases, SecretedMiceMice, KnockoutOligonucleotide Array Sequence AnalysisPulmonary AlveoliUp-RegulationConceptsIdiopathic pulmonary fibrosisHyperplastic epithelial cellsAlveolar epithelial cellsEpithelial cellsMMP-19IPF lungsWT miceLung fibrosisFibrotic responseHyperplastic alveolar epithelial cellsNovel mediatorLaser capture microscopeLung fibrotic responseDevelopment of fibrosisWild-type miceEpithelial phenotypic changesMatrix metalloproteinase-19Microarray analysisA549 epithelial cellsLung injuryBronchoalveolar lavagePulmonary fibrosisLung tissueSame lungFibrosis
2009
Clara Cells Attenuate the Inflammatory Response through Regulation of Macrophage Behavior
Snyder JC, Reynolds SD, Hollingsworth JW, Li Z, Kaminski N, Stripp BR. Clara Cells Attenuate the Inflammatory Response through Regulation of Macrophage Behavior. American Journal Of Respiratory Cell And Molecular Biology 2009, 42: 161-171. PMID: 19423773, PMCID: PMC2822978, DOI: 10.1165/rcmb.2008-0353oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChronic DiseaseFemaleIn Vitro TechniquesInterleukin-6LipopolysaccharidesLung DiseasesMacrophages, AlveolarMaleMiceMice, CongenicMice, Inbred C57BLMice, KnockoutNeutrophilsOligonucleotide Array Sequence AnalysisPneumoniaRNA, MessengerSignal TransductionToll-Like Receptor 4Tumor Necrosis Factor-alphaUteroglobinConceptsClara cell secretory proteinChronic lung diseaseCell secretory functionWild-type miceInflammatory responseClara cellsLung diseaseEpithelial remodelingGene expression analysisSecretory functionMacrophage behaviorTNF-alpha signalingLung inflammatory responsePolymorphonuclear leukocyte recruitmentTNF-alpha productionExpression analysisSecretory proteinsGenetic mouse modelsPseudomonas aeruginosa LPSPathway modelingCCSP deficiencyLung inflammationExcessive inflammationTNF-alphaAirway fluid
2008
Oxidative Stress Alters Syndecan-1 Distribution in Lungs with Pulmonary Fibrosis*
Kliment CR, Englert JM, Gochuico BR, Yu G, Kaminski N, Rosas I, Oury TD. Oxidative Stress Alters Syndecan-1 Distribution in Lungs with Pulmonary Fibrosis*. Journal Of Biological Chemistry 2008, 284: 3537-3545. PMID: 19073610, PMCID: PMC2635035, DOI: 10.1074/jbc.m807001200.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisLavage fluidNeutrophil chemotaxisSyndecan-1EC-SODSyndecan-1 ectodomainWound healingMouse lungNull miceWestern blotOxidative stressInterstitial lung diseaseBronchoalveolar lavage fluidShed syndecan-1Aberrant wound healingAlveolar epithelial cellsHuman lung samplesHuman syndecan-1Extracellular superoxide dismutaseEpithelial wound healingIPF lungsProgressive fibrosisLung fibrosisAlveolar epithelial wound healingCross 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 genesPatientsLungA Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis
Englert JM, Hanford LE, Kaminski N, Tobolewski JM, Tan RJ, Fattman CL, Ramsgaard L, Richards TJ, Loutaev I, Nawroth PP, Kasper M, Bierhaus A, Oury TD. A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis. American Journal Of Pathology 2008, 172: 583-591. PMID: 18245812, PMCID: PMC2258251, DOI: 10.2353/ajpath.2008.070569.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAdvanced glycation end productsRAGE-null micePulmonary fibrosisGlycation end productsIPF pathogenesisMouse modelNovel therapeutic targetHealthy adult animalsIPF patientsWild-type controlsDismal prognosisSevere fibrosisIPF tissueEffective therapyFibrotic lungsTherapeutic targetHistological scoringFibrosisLoss of RAGECell surface receptorsAdult animalsMiceEnd productsSoluble isoform
2007
A Functional and Regulatory Map of Asthma
Novershtern N, Itzhaki Z, Manor O, Friedman N, Kaminski N. A Functional and Regulatory Map of Asthma. American Journal Of Respiratory Cell And Molecular Biology 2007, 38: 324-336. PMID: 17921359, PMCID: PMC2258452, DOI: 10.1165/rcmb.2007-0151oc.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAllergensAnimalsAsthmaDisease Models, AnimalGene Expression ProfilingHumansHypersensitivityImmunity, InnateInterleukin-13MiceMice, Inbred AMice, Inbred BALB CMice, Inbred C3HMice, KnockoutModels, BiologicalOligonucleotide Array Sequence AnalysisOvalbuminProtein Interaction MappingReproducibility of ResultsSystems BiologyTranscription, GeneticTransforming Growth Factor beta1ConceptsCo-regulated gene modulesGene expression compendiumProtein interaction networksModule network analysisMouse microarray datasetsSystems-level viewExpression compendiumRegulatory mapGene modulesModule membersFunctional themesInteraction networksKey regulatorAnimal modelsMicroarray datasetsGeneral inductionAnnotation setsChronic inflammatory airway diseasesMorbidity of asthmaInflammatory airway diseasesMechanisms of asthmaAdaptive immune responsesSystem-level approachSimilar roleDistinct responses
2006
Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis
Wang XM, Zhang Y, Kim HP, Zhou Z, Feghali-Bostwick CA, Liu F, Ifedigbo E, Xu X, Oury TD, Kaminski N, Choi AM. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. Journal Of Experimental Medicine 2006, 203: 2895-2906. PMID: 17178917, PMCID: PMC1850940, DOI: 10.1084/jem.20061536.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBleomycinCaveolin 1Collagen Type IEpithelial CellsExtracellular MatrixFibroblastsFibronectinsFibrosisGene ExpressionHumansHydroxyprolineJNK Mitogen-Activated Protein KinasesLungMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 8PhosphorylationPulmonary FibrosisRNA, Small InterferingSmad2 ProteinTransfectionTransforming Growth Factor beta1ConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisCav-1 expressionCav-1Pulmonary fibroblastsPrimary pulmonary fibroblastsNovel therapeutic targetProgressive chronic disorderLung tissue samplesActivation of fibroblastsGrowth factor beta1Smad signaling cascadesHuman pulmonary fibroblastsC-Jun N-terminal kinase (JNK) pathwayIPF patientsLung fibrosisProfibrotic cytokinesChronic disordersN-terminal kinase pathwayLung tissueTherapeutic targetFibrosisHydroxyproline contentHistological analysisMarked reduction
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 growthIntegrinsExpression