2013
Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice
Leikauf GD, Concel VJ, Bein K, Liu P, Berndt A, Martin TM, Ganguly K, Jang AS, Brant KA, Dopico RA, Upadhyay S, Cario C, Di YP, Vuga LJ, Kostem E, Eskin E, You M, Kaminski N, Prows DR, Knoell DL, Fabisiak JP. Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice. American Journal Of Respiratory Cell And Molecular Biology 2013, 49: 130522202035005. PMID: 23590305, PMCID: PMC3824050, DOI: 10.1165/rcmb.2012-0337oc.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAllelesAnimalsChemical Warfare AgentsChromosome MappingElectrophoretic Mobility Shift AssayFemaleGene ExpressionGene Expression ProfilingGenomeGenome-Wide Association StudyGenomicsGenotypeIntegrinsLungMiceMice, Inbred StrainsOligonucleotide Array Sequence AnalysisPhosgenePolymorphism, Single NucleotidePromoter Regions, GeneticReelin ProteinSodium-Potassium-Exchanging ATPaseConceptsSignificant SNP associationsSNP associationsTranscriptomic analysisCompetitive electrophoretic mobility shift analysisGenome-wide association mappingFunctional genomic assessmentPutative transcription factorElectrophoretic mobility shift analysisMobility shift analysisAssociation mappingGenetic resolutionTranscription factorsCandidate genesFunctional domainsNonsynonymous SNPsGenomic assessmentPhenotypic differencesPhenotypic extremesDiverse panelGenesGenetic determinantsShift analysisPTPRTAllelesITGA9
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
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
2000
Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis
Kaminski N, Allard J, Pittet J, Zuo F, Griffiths M, Morris D, Huang X, Sheppard D, Heller R. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 1778-1783. PMID: 10677534, PMCID: PMC26512, DOI: 10.1073/pnas.97.4.1778.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisLung inflammationBleomycin administrationSusceptible miceMultiple time pointsFibrotic responseFibrosisFibrotic diseasesInflammationMore effective strategiesGene expressionTime pointsMiceBeta6 subunitMolecular mechanismsSequential inductionGene expression patternsExpression patternsNull mutationResponseEffective strategyLungExpressionBleomycinGene expression programs
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