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 ResearchConceptsIdiopathic 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 efficacyBronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro
Uthaya Kumar DB, Motakis E, Yurieva M, Kohar V, Martinek J, Wu TC, Khoury J, Grassmann J, Lu M, Palucka K, Kaminski N, Koff JL, Williams A. Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2022, 322: l822-l841. PMID: 35438006, PMCID: PMC9142163, DOI: 10.1152/ajplung.00254.2021.Peer-Reviewed Original ResearchConceptsProtein codingEpithelial-mesenchymal transitionLncRNA genesEMT inductionSingle-cell RNA sequencingSingle-cell RNA-seq dataEpithelial-mesenchymal plasticityRNA-seq dataMechanisms of EMTSingle-cell levelEpithelial cell typesRole of EMTTranscriptional reprogrammingHuman bronchial epithelial cellsRNA genesEMT gene signatureTranscriptional changesTranscriptional differencesRNA sequencingSpecific lncRNAsBronchial epithelial cellsDifferential expressionMyofibroblast conversionCell typesGenes
2014
Matrix Metalloproteinase-19 Promotes Metastatic Behavior In Vitro and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer
Yu G, Herazo-Maya JD, Nukui T, Romkes M, Parwani A, Juan-Guardela BM, Robertson J, Gauldie J, Siegfried JM, Kaminski N, Kass DJ. Matrix Metalloproteinase-19 Promotes Metastatic Behavior In Vitro and Is Associated with Increased Mortality in Non–Small Cell Lung Cancer. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 780-790. PMID: 25250855, PMCID: PMC4299607, DOI: 10.1164/rccm.201310-1903oc.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerEpithelial-mesenchymal transitionLung tumorsMatrix metalloproteinasesProgression of NSCLCNormal lung tissuesHuman lung cancerNSCLC cell linesMultiple NSCLC cell linesLung cancer tumorsMMP19 expressionPoor prognosisCancer deathControl subjectsIncreased MortalityLung tissueNSCLC cellsMolecular pathogenesisPotential biomarkersDisease severityMetastatic behaviorCancerCancer tumors
2012
Zyxin Is a Transforming Growth Factor-β (TGF-β)/Smad3 Target Gene That Regulates Lung Cancer Cell Motility via Integrin α5β1*
Mise N, Savai R, Yu H, Schwarz J, Kaminski N, Eickelberg O. Zyxin Is a Transforming Growth Factor-β (TGF-β)/Smad3 Target Gene That Regulates Lung Cancer Cell Motility via Integrin α5β1*. Journal Of Biological Chemistry 2012, 287: 31393-31405. PMID: 22778267, PMCID: PMC3438968, DOI: 10.1074/jbc.m112.357624.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Adhesion MoleculesCell Line, TumorCell MovementFocal AdhesionsGene SilencingHumansIntegrin alpha5beta1Intercellular JunctionsLung NeoplasmsMiceMice, Mutant StrainsMicrofilament ProteinsPhosphoproteinsProto-Oncogene Proteins p21(ras)Signal TransductionSmad3 ProteinTransforming Growth Factor beta1ZyxinConceptsEpithelial-mesenchymal transitionCancer cell motilityCell motilityFocal adhesionsZyxin expressionCell-extracellular matrix adhesionLung cancer cellsFocal adhesion proteinsSingle cell motilityCell-cell junctionsCell adherens junctionsNovel functional targetSingle cell migrationLung cancer cell motilityCancer cellsNovel direct targetZyxin geneTGF-β signalingTumor suppressor effectActin cytoskeletonAdherens junctionsCytoskeletal organizationZyxinTarget genesAdhesion proteins
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 lungFibrosisMicroRNAs in idiopathic pulmonary fibrosis
Pandit KV, Milosevic J, Kaminski N. MicroRNAs in idiopathic pulmonary fibrosis. Translational Research 2011, 157: 191-199. PMID: 21420029, DOI: 10.1016/j.trsl.2011.01.012.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIPF lungsPulmonary fibrosisLung fibrosisMiR-155Vascular endothelial growth factor (VEGF) pathwayEndothelial growth factor pathwayLethal fibrotic lung diseaseFibrotic lung diseaseMiR-29Upregulated miR-155Growth factor-β1Epithelial-mesenchymal transitionGrowth factor pathwaysLung epithelial cellsLung diseaseProfibrotic effectsBleomycin modelRole of microRNAsTherapeutic targetFactor-β1FibrosisMesenchymal transitionFactor pathwayLet-7 family members