Featured Publications
A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis
Chioccioli M, Roy S, Newell R, Pestano L, Dickinson B, Rigby K, Herazo-Maya J, Jenkins G, Ian S, Saini G, Johnson SR, Braybrooke R, Yu G, Sauler M, Ahangari F, Ding S, DeIuliis J, Aurelien N, Montgomery RL, Kaminski N. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. EBioMedicine 2022, 85: 104304. PMID: 36265417, PMCID: PMC9587275, DOI: 10.1016/j.ebiom.2022.104304.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNon-human primatesPulmonary fibrosisAnimal modelsPro-fibrotic genesAnti-fibrotic efficacyMiR-29 mimicsHuman peripheral bloodMiR-29b levelsHuman lung fibroblastsIPF patientsIPF diagnosisPeripheral bloodReduced fibrosisAdverse findingsPotential therapyLung slicesTGF-β1Relevant dosesLung fibroblastsNIH-NHLBIFibrosisTherapyCollagen productionProfibrotic gene program
2023
SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis
Barbayianni I, Kanellopoulou P, Fanidis D, Nastos D, Ntouskou E, Galaris A, Harokopos V, Hatzis P, Tsitoura E, Homer R, Kaminski N, Antoniou K, Crestani B, Tzouvelekis A, Aidinis V. SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis. Nature Communications 2023, 14: 5882. PMID: 37735172, PMCID: PMC10514346, DOI: 10.1038/s41467-023-41614-x.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisExtracellular matrix invasionLung fibroblastsIdiopathic pulmonary fibrosis patientsIdiopathic pulmonary fibrosisPulmonary fibrosis patientsMatrix invasionPromising therapeutic optionProfibrotic milieuTherapeutic optionsLung tissuePathogenic hallmarkPharmacological targetingFibrosisFibrosis patientsIncurable diseaseEx vivoBleomycinExtracellular matrix componentsTks5 expressionAberrant depositionInvasionMiceFibroblastsSrc kinase
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 efficacy
2019
Role 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
2017
Loss 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
Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies
Tan J, Tedrow JR, Dutta JA, Juan-Guardela B, Nouraie M, Chu Y, Trejo Bittar H, Ramani K, Biswas PS, Veraldi KL, Kaminski N, Zhang Y, Kass DJ. Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies. American Journal Of Respiratory And Critical Care Medicine 2016, 194: 1392-1402. PMID: 27310652, PMCID: PMC5148141, DOI: 10.1164/rccm.201509-1865oc.Peer-Reviewed Original ResearchConceptsRelaxin/insulin-like family peptide receptor 1Idiopathic pulmonary fibrosisIPF lung fibroblastsRXFP1 expressionLung fibroblastsPulmonary fibrosisFamily peptide receptor 1RXFP1 gene expressionLung Tissue Research ConsortiumPulmonary functionIPF lungsBleomycin injuryPotential therapyCollagen depositionFibrotic diseasesPatientsDemographic dataPotential efficacyReceptor 1Donor controlsTherapyRelaxin-like peptideGrowth factorGene expressionFibrosisSH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis
Tzouvelekis A, Yu G, Lino Cardenas CL, Herazo-Maya JD, Wang R, Woolard T, Zhang Y, Sakamoto K, Lee H, Yi JS, DeIuliis G, Xylourgidis N, Ahangari F, Lee PJ, Aidinis V, Herzog EL, Homer R, Bennett AM, Kaminski N. SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2016, 195: 500-514. PMID: 27736153, PMCID: PMC5378419, DOI: 10.1164/rccm.201602-0329oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisProfibrotic stimuliLung fibroblastsChronic fatal lung diseaseMyofibroblast differentiationPrimary human lung fibroblastsFatal lung diseaseNovel therapeutic strategiesVivo therapeutic effectPotential therapeutic usefulnessHuman lung fibroblastsMouse lung fibroblastsDismal prognosisFibroblastic fociLung fibrosisLung diseaseBleomycin modelTherapeutic effectTherapeutic usefulnessTherapeutic strategiesTherapeutic targetTransgenic miceFibrosisSHP2 overexpression
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
Let-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
Cartilage Oligomeric Matrix Protein in Idiopathic Pulmonary Fibrosis
Vuga LJ, Milosevic J, Pandit K, Ben-Yehudah A, Chu Y, Richards T, Sciurba J, Myerburg M, Zhang Y, Parwani AV, Gibson KF, Kaminski N. Cartilage Oligomeric Matrix Protein in Idiopathic Pulmonary Fibrosis. PLOS ONE 2013, 8: e83120. PMID: 24376648, PMCID: PMC3869779, DOI: 10.1371/journal.pone.0083120.Peer-Reviewed Original ResearchMeSH KeywordsAgedCartilage Oligomeric Matrix ProteinCells, CulturedCollagen Type ICollagen Type I, alpha 1 ChainExtracellular MatrixFemaleFibroblastsGene Expression RegulationHumansIdiopathic Pulmonary FibrosisLungMaleMiddle AgedPlasminogen Activator Inhibitor 1RNA, Small InterferingSignal TransductionSmad3 ProteinTransforming Growth Factor beta1VimentinConceptsIdiopathic pulmonary fibrosisCartilage oligomeric matrix proteinIPF lungsNormal human lung fibroblastsForce vital capacityHuman lung fibroblastsTGF-β1Oligomeric matrix proteinPulmonary fibrosisLung fibroblastsSerum COMP concentrationTGF-β1 activityEpithelial cell hyperplasiaMatrix proteinsLung restrictionWestern blot analysisExtracellular matrix depositionIPF patientsTime-dependent fashionDisease activityMedian survivalVital capacityCell hyperplasiaControl lungsBlood drawmiR-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
2012
Profibrotic Role of miR-154 in Pulmonary Fibrosis
Milosevic J, Pandit K, Magister M, Rabinovich E, Ellwanger DC, Yu G, Vuga LJ, Weksler B, Benos PV, Gibson KF, McMillan M, Kahn M, Kaminski N. Profibrotic Role of miR-154 in Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2012, 47: 879-887. PMID: 23043088, PMCID: PMC3547095, DOI: 10.1165/rcmb.2011-0377oc.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesCell MovementCell ProliferationCells, CulturedChromosomes, Human, Pair 14Cyclin-Dependent Kinase Inhibitor p15FibroblastsGene ExpressionHumansLungMicroRNAsMultigene FamilyOligonucleotide Array Sequence AnalysisPulmonary FibrosisRNA InterferenceTranscriptomeTransforming Growth Factor beta1Wnt Signaling PathwayConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsMiR-154IPF lungsPulmonary fibrosisIPF fibroblastsProgressive interstitial lung diseaseInterstitial lung diseaseWnt/β-catenin pathwayHuman lung fibroblastsΒ-catenin pathwayTGF-β1 stimulationBinding of Smad3Quantitative RT-PCRLung diseaseProfibrotic roleExpression of microRNAsICG-001MiR-134Unknown originMiR-382MiR-487bProliferative effectLung fibroblastsMiR-410
2011
Genomic Differences Distinguish the Myofibroblast Phenotype of Distal Lung Fibroblasts from Airway Fibroblasts
Zhou X, Wu W, Hu H, Milosevic J, Konishi K, Kaminski N, Wenzel SE. Genomic Differences Distinguish the Myofibroblast Phenotype of Distal Lung Fibroblasts from Airway Fibroblasts. American Journal Of Respiratory Cell And Molecular Biology 2011, 45: 1256-1262. PMID: 21757679, PMCID: PMC3262668, DOI: 10.1165/rcmb.2011-0065oc.Peer-Reviewed Original ResearchConceptsGenomic differencesMicroarray analysisC-Jun N-terminal kinaseExtracellular matrix-associated moleculesMyofibroblast-like characteristicsDistinct genomic differencesN-terminal kinasePotential functional implicationsQuantitative real-time PCRMatrix-associated moleculesCytoskeletal organizationGene OntologyActin bindingLung fibroblastsReal-time PCRMyofibroblast phenotypeFunctional implicationsParenchymal fibroblastsAirway fibroblastsDifferentiated fibroblastsPathway activationDifferent phenotypesRegional fibroblastsFibroblastsPhenotype
2009
WNT5A Is a Regulator of Fibroblast Proliferation and Resistance to Apoptosis
Vuga LJ, Ben-Yehudah A, Kovkarova-Naumovski E, Oriss T, Gibson KF, Feghali-Bostwick C, Kaminski N. WNT5A Is a Regulator of Fibroblast Proliferation and Resistance to Apoptosis. American Journal Of Respiratory Cell And Molecular Biology 2009, 41: 583-589. PMID: 19251946, PMCID: PMC2778165, DOI: 10.1165/rcmb.2008-0201oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBeta CateninBlotting, WesternCase-Control StudiesCaspase 3Cell LineCell ProliferationCell SurvivalFibroblastsFibronectinsGene Expression ProfilingHumansHydrogen PeroxideIdiopathic Pulmonary FibrosisIntegrin alpha5LungMiceOligonucleotide Array Sequence AnalysisProto-Oncogene ProteinsRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionRNA InterferenceTransfectionUp-RegulationWnt ProteinsWnt-5a ProteinConceptsUsual interstitial pneumoniaNormal lung fibroblastsLung tissueLung fibroblastsFibrotic interstitial lung diseaseInterstitial lung fibrosisSpecific histopathologic patternIdiopathic pulmonary fibrosisInterstitial lung diseaseRole of Wnt5aReal-time RT-PCRQuantitative real-time RT-PCRInterstitial pneumoniaPulmonary fibrosisAutoimmune diseasesHistopathologic patternLung diseaseLung fibrosisHistological patternNormal histologyWnt/beta-catenin pathwayCanonical Wnt/beta-catenin pathwayWestern blotFibroblast proliferationBeta-catenin pathway
2001
Interleukin-13 Induces Dramatically Different Transcriptional Programs in Three Human Airway Cell Types
Lee J, Kaminski N, Dolganov G, Grunig G, Koth L, Solomon C, Erle D, Sheppard D. Interleukin-13 Induces Dramatically Different Transcriptional Programs in Three Human Airway Cell Types. American Journal Of Respiratory Cell And Molecular Biology 2001, 25: 474-485. PMID: 11694453, DOI: 10.1165/ajrcmb.25.4.4522.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedEndopeptidasesExtracellular Matrix ProteinsFibroblastsGene Expression RegulationHumansInterleukin-13Ion ChannelsMuscle, SmoothOligonucleotide Array Sequence AnalysisProtease InhibitorsRespiratory MucosaRespiratory SystemSignal TransductionSTAT6 Transcription FactorTrans-ActivatorsTranscription, GeneticConceptsAirway cell typesIL-13Airway epithelial cellsAirway cellsAirway smooth muscle cellsPhenotypic featuresInterleukin-13 inducesResident airway cellsEpithelial cellsImmediate hypersensitivity responsesAirway smooth muscleDevelopment of asthmaCell typesSmooth muscle cellsHypersensitivity responseT lymphocytesSmooth muscleAsthmaB lymphocytesLung fibroblastsMuscle cellsVivo responseCentral mediatorGene expressionPrimary cultures