2022
Microenvironmental 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 forces
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 fibrogenesisLong noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state
Omote N, Sakamoto K, Li Q, Schupp JC, Adams T, Ahangari F, Chioccioli M, DeIuliis G, Hashimoto N, Hasegawa Y, Kaminski N. Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state. Physiological Reports 2021, 9: e14727. PMID: 33527707, PMCID: PMC7851438, DOI: 10.14814/phy2.14727.Peer-Reviewed Original ResearchConceptsTerminal differentiation-induced lncRNANormal human bronchial epithelial cellsTINCR overexpressionCell differentiationNotch genesTissue developmentBronchial epithelial cellsExtracellular matrix organizationCell phenotypeRNA sequencing analysisNumerous biological functionsRole of lncRNAsCell differentiation stateEpithelial cellsHuman bronchial epithelial cellsCiliated cell differentiationStaufen1 proteinNovel regulatorBasal cell phenotypeDownstream regulatorsRNA immunoprecipitationBiological functionsCritical regulatorDifferential expressionDifferentiation state
2018
PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production
Celada LJ, Kropski JA, Herazo-Maya JD, Luo W, Creecy A, Abad AT, Chioma OS, Lee G, Hassell NE, Shaginurova GI, Wang Y, Johnson JE, Kerrigan A, Mason WR, Baughman RP, Ayers GD, Bernard GR, Culver DA, Montgomery CG, Maher TM, Molyneaux PL, Noth I, Mutsaers SE, Prele CM, Peebles R, Newcomb DC, Kaminski N, Blackwell TS, Van Kaer L, Drake WP. PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Science Translational Medicine 2018, 10 PMID: 30257954, PMCID: PMC6263177, DOI: 10.1126/scitranslmed.aar8356.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsBleomycinCD4-Positive T-LymphocytesCell ProliferationCollagen Type IDisease Models, AnimalFemaleFibroblastsGene Expression RegulationHumansIdiopathic Pulmonary FibrosisInterleukin-17MaleMiceMiddle AgedProgrammed Cell Death 1 ReceptorRNA, MessengerSarcoidosisSTAT3 Transcription FactorTh17 CellsTransforming Growth Factor beta1Up-RegulationConceptsIdiopathic pulmonary fibrosisPD-1Pulmonary fibrosisT cellsCollagen-1 productionPD-1 pathway blockadeCell death ligand 1T helper 17 (Th17) cellsPD-1 regulationIL-17A expressionProgressive inflammatory diseaseDeath ligand 1Helper 17 cellsT cell subsetsCell death 1Limited therapeutic optionsTGF-β1 productionLung disease pathophysiologyHuman lung fibroblastsPredominant CD4Bleomycin administrationIL-17ADeath-1Therapeutic optionsCell subsets
2017
Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis
Hawkins C, Shaginurova G, Shelton DA, Herazo-Maya JD, Oswald-Richter KA, Rotsinger JE, Young A, Celada LJ, Kaminski N, Sevin C, Drake WP. Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis. Journal Of Immunology Research 2017, 2017: 3642832. PMID: 29234685, PMCID: PMC5695030, DOI: 10.1155/2017/3642832.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedApoptosisCD4-Positive T-LymphocytesCell ProliferationCells, CulturedClonal AnergyCytokinesDisease ProgressionFemaleGene Expression RegulationHumansLymphocyte ActivationMaleMiddle AgedProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-Cell, alpha-betaSarcoidosis, PulmonaryTh1 CellsYoung AdultConceptsT cell exhaustionTh1 cytokine expressionPD-1 expressionCell exhaustionCytokine expressionT cellsHealthy controlsInhibitory cell surface receptorsT cell immune functionTh1 immune responseChronic antigenic stimulationCell immune functionProliferative capacityT cell functionSarcoidosis subjectsSystemic CD4Pulmonary sarcoidosisDisease resolutionProgressive diseaseClinical resolutionCytokine productionAntigenic stimulationDisease progressionImmune responseCD4
2015
Regulation of alveolar septation by microRNA-489
Olave N, Lal CV, Halloran B, Pandit K, Cuna AC, Faye-Petersen OM, Kelly DR, Nicola T, Benos PV, Kaminski N, Ambalavanan N. Regulation of alveolar septation by microRNA-489. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2015, 310: l476-l487. PMID: 26719145, PMCID: PMC4773841, DOI: 10.1152/ajplung.00145.2015.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaMiR-489Alveolar septationLung developmentInsulin-like growth factor-1Abnormal lung developmentGrowth factor-1MiR-489 overexpressionNormal pretermTerm infantsC57BL/6 miceMouse lung developmentTherapeutic strategiesMiRNA-489HyperoxiaEpithelial originFurther inhibitionIGF1Factor 1MiRNA antagonistsNormoxiaTenascin CMiRNA profilesCytomegalovirus promoterInfantsVCAM-1 is a TGF-β1 inducible gene upregulated in idiopathic pulmonary fibrosis
Agassandian M, Tedrow JR, Sembrat J, Kass DJ, Zhang Y, Goncharova EA, Kaminski N, Mallampalli RK, Vuga LJ. VCAM-1 is a TGF-β1 inducible gene upregulated in idiopathic pulmonary fibrosis. Cellular Signalling 2015, 27: 2467-2473. PMID: 26386411, PMCID: PMC4684430, DOI: 10.1016/j.cellsig.2015.09.003.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisVCAM-1IPF subjectsPulmonary fibrosisVascular cell adhesion molecule-1Lethal interstitial lung diseaseVCAM-1 protein levelsCell adhesion molecule-1Interstitial lung diseaseLungs of subjectsProtein levelsHigher plasma levelsVCAM-1 mRNAAdhesion molecule-1Pulmonary diffusion capacityHuman lung fibroblastsIPF lungsLung functionFibrotic fociVital capacityLung diseaseUnknown etiologyControl subjectsPlasma levelsCell cycle arrestMatrix 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
Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity
Braun NA, Celada LJ, Herazo-Maya JD, Abraham S, Shaginurova G, Sevin CM, Grutters J, Culver DA, Dworski R, Sheller J, Massion PP, Polosukhin VV, Johnson JE, Kaminski N, Wilkes DS, Oswald-Richter KA, Drake WP. Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 560-571. PMID: 25073001, PMCID: PMC4214083, DOI: 10.1164/rccm.201401-0188oc.Peer-Reviewed Original ResearchConceptsPD-1 pathway blockadeT cell proliferative capacityPeripheral blood mononuclear cellsPD-L1 expressionPD-1 pathwayBlood mononuclear cellsT cell functionPathway blockadePD-L1Clinical outcomesLung diseaseMononuclear cellsControl subjectsProliferative capacityT cellsImmunohistochemistry analysisPD-1/PD-L1 expressionControl peripheral blood mononuclear cellsHealthy control peripheral blood mononuclear cellsHealthy control lungsIdiopathic lung diseaseSpontaneous clinical resolutionChronic lung diseaseHealthy control subjectsEffective therapeutic interventionsLet-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
Reconstructing dynamic microRNA-regulated interaction networks
Schulz MH, Pandit KV, Cardenas C, Ambalavanan N, Kaminski N, Bar-Joseph Z. Reconstructing dynamic microRNA-regulated interaction networks. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 15686-15691. PMID: 23986498, PMCID: PMC3785769, DOI: 10.1073/pnas.1303236110.Peer-Reviewed Original ResearchConceptsTranscription factorsGene expressionDynamic Regulatory Events MinerTemporal gene expressionDynamic regulatory networksSpecific developmental phasesMRNA expression dataLung developmentRegulatory networksMiRNA targetsInteraction networksImportant miRNAsExpression dataMiRNAsAdditional miRNAsLung differentiationDevelopmental phasesMiRNAPostnatal lung developmentProgression pathwaysProliferation assaysExpressionRegulationMRNA expressionMicroRNAsmiR-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
The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets†
Pode‐Shakked N, Shukrun R, Mark‐Danieli M, Tsvetkov P, Bahar S, Pri‐Chen S, Goldstein RS, Rom‐Gross E, Mor Y, Fridman E, Meir K, Simon A, Magister M, Kaminski N, Goldmacher VS, Harari‐Steinberg O, Dekel B. The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets†. EMBO Molecular Medicine 2012, 5: 18-37. PMID: 23239665, PMCID: PMC3569651, DOI: 10.1002/emmm.201201516.Peer-Reviewed Original ResearchMeSH KeywordsAC133 AntigenAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAnimalsAntibodies, MonoclonalAntigens, CDCD56 AntigenCell DifferentiationCell ProliferationCell SeparationGene ExpressionGlycoproteinsHumansKidney NeoplasmsMaytansineMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsPeptidesRetinal DehydrogenaseTumor Cells, CulturedTumor Stem Cell AssayWilms TumorXenograft Model Antitumor AssaysConceptsNew therapeutic targetsTherapeutic targetPediatric solid tumorsPoor patient prognosisCancer initiating cellsMultiple xenograft modelsHuman WilmsCancer stem cellsAldehyde dehydrogenase activityMiR-200 familyPrimary tumorPatient prognosisRenal malignancyImmunodeficient micePediatric cancerXenograft modelTumor xenograftsXenograft cellsSolid tumorsTumor biologyComplete eradicationPediatric renal malignancyInitiating cellsProtein expressionTumorsProfibrotic 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
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
2008
Idiopathic Pulmonary Fibrosis: Aberrant Recapitulation of Developmental Programs?
Selman M, Pardo A, Kaminski N. Idiopathic Pulmonary Fibrosis: Aberrant Recapitulation of Developmental Programs? PLOS Medicine 2008, 5: e62. PMID: 18318599, PMCID: PMC2265304, DOI: 10.1371/journal.pmed.0050062.Peer-Reviewed Original Research
2007
Cellular and Humoral Autoreactivity in Idiopathic Pulmonary Fibrosis
Feghali-Bostwick CA, Tsai CG, Valentine VG, Kantrow S, Stoner MW, Pilewski JM, Gadgil A, George MP, Gibson KF, Choi AM, Kaminski N, Zhang Y, Duncan SR. Cellular and Humoral Autoreactivity in Idiopathic Pulmonary Fibrosis. The Journal Of Immunology 2007, 179: 2592-2599. PMID: 17675522, DOI: 10.4049/jimmunol.179.4.2592.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCD4 T cellsT cellsIPF patientsAutoantibody productionPulmonary fibrosisEffector functionsProliferative responseAutologous CD4 T cellsLung extractsPeripheral CD4 T lymphocytesPeripheral CD4 T cellsT cell clonal expansionAutoreactive immune processesAdaptive immune mechanismsCD4 T lymphocytesMHC class IIMore effective therapiesCell clonal expansionCycles of stimulationHumoral autoreactivityOligoclonal expansionPathologic responseIL-10Hilar lymph
2005
Up-Regulation and Profibrotic Role of Osteopontin in Human Idiopathic Pulmonary Fibrosis
Pardo A, Gibson K, Cisneros J, Richards TJ, Yang Y, Becerril C, Yousem S, Herrera I, Ruiz V, Selman M, Kaminski N. Up-Regulation and Profibrotic Role of Osteopontin in Human Idiopathic Pulmonary Fibrosis. PLOS Medicine 2005, 2: e251. PMID: 16128620, PMCID: PMC1198037, DOI: 10.1371/journal.pmed.0020251.Peer-Reviewed Original ResearchMeSH KeywordsBronchoalveolar Lavage FluidCell MovementCell ProliferationCells, CulturedEpithelial CellsExtracellular MatrixFemaleGene Expression ProfilingHumansLungMaleMatrix Metalloproteinase 1Matrix Metalloproteinase 7Middle AgedMolecular Sequence DataOsteopontinPulmonary FibrosisRecombinant ProteinsSialoglycoproteinsTissue Inhibitor of Metalloproteinase-1Up-RegulationConceptsIdiopathic pulmonary fibrosisAlveolar epithelial cellsIPF lungsMMP-7Pulmonary fibrosisEpithelial cellsHuman idiopathic pulmonary fibrosisHuman IPF lungsPrimary human lung fibroblastsMatrix metalloprotease-1 expressionMetalloprotease-1 expressionHuman lung fibroblastsIPF patientsBronchoalveolar lavageProfibrotic effectsProfibrotic roleNormal lungAlveolar epitheliumTissue inhibitorTherapeutic interventionsAnti-CD44Incurable diseaseLungMetalloprotease-1Lethal disorder