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
2021
Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project
Camp R, Smith ML, Larsen BT, Roden AC, Farver C, Moreira AL, Attanoos R, Pillappa R, Sansano I, Fabro AT, Homer RJ. Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project. BMC Pulmonary Medicine 2021, 21: 184. PMID: 34074264, PMCID: PMC8170950, DOI: 10.1186/s12890-021-01522-6.Peer-Reviewed Original ResearchConceptsFibrotic ILDInterobserver variationHistopathologic diagnosisUsual interstitial pneumonia/idiopathic pulmonary fibrosisFibrotic interstitial lung diseaseCurrent histopathologic criteriaUIP/IPFIdiopathic pulmonary fibrosisInterstitial lung diseaseDiagnosis of ILDExtent of inflammationPattern of fibrosisSignificant interobserver variationSpecific diagnostic featuresILD evaluationPulmonary fibrosisLung diseaseHistopathologic evaluationHistopathologic criteriaDiagnostic guidelinesTissue-based diagnosticsDiagnosisILDFibrosisInternet-based approachesMacrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. Journal Of Clinical Investigation 2021, 131: e136542. PMID: 33393489, PMCID: PMC7773383, DOI: 10.1172/jci136542.Peer-Reviewed Original ResearchConceptsNetrin-1Lung fibrosisCell-specific knockout miceΑ1-adrenoreceptor blockadeIPF lung tissueNeuronal guidance proteinsNetrin-1 expressionExtracellular matrix accumulationAdrenergic processesAdrenoreceptor antagonismAdrenoreceptor blockadeFibrotic histologyInflammatory scarringIPF cohortAdrenergic nervesΑ1-blockersImproved survivalColorectal carcinomaLung tissueKnockout miceCollagen accumulationFibrosisMatrix accumulationMacrophagesGuidance proteins
2020
Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis
Adams TS, Schupp JC, Poli S, Ayaub EA, Neumark N, Ahangari F, Chu SG, Raby BA, DeIuliis G, Januszyk M, Duan Q, Arnett HA, Siddiqui A, Washko GR, Homer R, Yan X, Rosas IO, Kaminski N. Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis. Science Advances 2020, 6: eaba1983. PMID: 32832599, PMCID: PMC7439502, DOI: 10.1126/sciadv.aba1983.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisVascular endothelial cellsIPF lungsPulmonary fibrosisChronic obstructive pulmonary disease (COPD) lungsFatal interstitial lung diseaseEndothelial cellsInterstitial lung diseaseCell populationsIPF myofibroblastsMyofibroblast fociNonsmoker controlsLung diseaseCOPD lungsBasaloid cellsSingle-cell atlasInvasive fibroblastsMacrophage populationsLungStromal cellsEpithelial cellsFibrosisCellular populationsDevelopmental markersSingle-cell RNA-seq
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 models
2017
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
2016
SH2 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 overexpressionPlexin 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
2014
Pulmonary Fibrosis
Murray L, Homer R, Gulati M, Herzog E. Pulmonary Fibrosis. 2014, 2636-2653. DOI: 10.1016/b978-0-12-386456-7.05307-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInterstitial lung diseasePulmonary fibrosisLung fibrosisConnective tissue disease-related interstitial lung diseaseIdiopathic pulmonary fibrosisSalient clinical featuresDistinctive pathological featuresWound healing responseClinical featuresChronic injuryLung diseasePathological featuresCirculating BiomarkersInflammatory responseLung parenchymaCertain therapiesPathogenic mechanismsScar tissueClinical monitoringFibrosisHealing responseFatal natureGenetic formsDiseasePotential role
2012
Chronic inflammation and lung fibrosis: pleotropic syndromes but limited distinct phenotypes
Gifford AH, Matsuoka M, Ghoda LY, Homer RJ, Enelow RI. Chronic inflammation and lung fibrosis: pleotropic syndromes but limited distinct phenotypes. Mucosal Immunology 2012, 5: 480-484. PMID: 22806097, DOI: 10.1038/mi.2012.68.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisClinical entityHypersensitivity pneumonitisLung diseaseLung fibrosisDifferent clinical presentationsDistinct phenotypesPostinflammatory fibrosisClinical presentationRheumatoid arthritisChronic inflammationClinical syndromeTherapeutic responseClinical diseaseMultiple potential reasonsFibrosisFibrotic phenotypeExperimental modelDiseaseSyndromeMatrix depositionPhenotypePhenotypic distinctionPneumonitis
2011
Role of semaphorin 7a signaling in transforming growth factor β1–induced lung fibrosis and scleroderma‐related interstitial lung disease
Gan Y, Reilkoff R, Peng X, Russell T, Chen Q, Mathai SK, Homer R, Gulati M, Siner J, Elias J, Bucala R, Herzog E. Role of semaphorin 7a signaling in transforming growth factor β1–induced lung fibrosis and scleroderma‐related interstitial lung disease. Arthritis & Rheumatism 2011, 63: 2484-2494. PMID: 21484765, PMCID: PMC3651701, DOI: 10.1002/art.30386.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsInterstitial lung diseaseBone marrow-derived cellsMarrow-derived cellsSemaphorin 7AGrowth factor-β1Lung diseaseLung fibrosisFactor-β1Human peripheral blood mononuclear cellsNormal human peripheral blood mononuclear cellsSemaphorin 7a expressionBone marrow transplantationBlood mononuclear cellsReceptor β1 integrinΒ1 integrinFibrocyte differentiationMarrow transplantationPulmonary fibrosisMononuclear cellsProfibrotic effectsTGFβ1 geneMurine modelFibrosisTissue accumulationModern concepts on the role of inflammation in pulmonary fibrosis.
Homer RJ, Elias JA, Lee CG, Herzog E. Modern concepts on the role of inflammation in pulmonary fibrosis. Archives Of Pathology & Laboratory Medicine 2011, 135: 780-8. PMID: 21631273, DOI: 10.5858/2010-0296-ra.1.BooksConceptsRole of inflammationIdiopathic pulmonary fibrosisPulmonary fibrosisTherapeutic interventionsResult of inflammationCell deathLung transplantationCytokine environmentMacrophage polarizationInflammationFibrosisLethal diseaseLimited biomarkersClinical contextDisease biomarkersBiomarkersDeathInterventionUnpublished researchTransplantationLungDisease
2010
Recent advances in pulmonary fibrosis: implications for scleroderma
Homer RJ, Herzog EL. Recent advances in pulmonary fibrosis: implications for scleroderma. Current Opinion In Rheumatology 2010, 22: 683-689. PMID: 20693906, DOI: 10.1097/bor.0b013e32833ddcc9.BooksConceptsPulmonary fibrosisEpithelial cell injuryCell injuryIdiopathic pulmonary fibrosisRole of lymphocytesAlternative macrophage activationPathogenesis of sclerodermaTranslational human studiesEpithelial-mesenchymal transitionEndoplasmic reticulum stressMost patientsSystemic sclerosisLung fibrosisLymphocyte functionEffective therapyLeading causeLung parenchymaFibrotic responseHuman studiesMacrophage activationScar tissueFibrosisPossible associationAnimal modelingPatientsInhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4
Jiang D, Liang J, Campanella GS, Guo R, Yu S, Xie T, Liu N, Jung Y, Homer R, Meltzer EB, Li Y, Tager AM, Goetinck PF, Luster AD, Noble PW. Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4. Journal Of Clinical Investigation 2010, 120: 2049-2057. PMID: 20484822, PMCID: PMC2877927, DOI: 10.1172/jci38644.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisCXCL10 proteinAcute lung injuryExcess extracellular matrix productionLung fibroblast migrationSyndecan-4Myofibroblast recruitmentLung injuryLung functionSubsequent fibrosisNeutrophil recruitmentInterstitial fibrosisWT miceIntratracheal instillationSyndecan-4 expressionNovel therapiesMigration of fibroblastsFibrosisBleomycin treatmentCXCL10Fibroblast recruitmentExtracellular matrix productionHeparan sulfate proteoglycan syndecan-4Interstitial compartmentMice
2007
Transforming Growth Factor (TGF)-β1 Stimulates Pulmonary Fibrosis and Inflammation via a Bax-dependent, Bid-activated Pathway That Involves Matrix Metalloproteinase-12*
Kang HR, Cho SJ, Lee CG, Homer RJ, Elias JA. Transforming Growth Factor (TGF)-β1 Stimulates Pulmonary Fibrosis and Inflammation via a Bax-dependent, Bid-activated Pathway That Involves Matrix Metalloproteinase-12*. Journal Of Biological Chemistry 2007, 282: 7723-7732. PMID: 17209037, DOI: 10.1074/jbc.m610764200.Peer-Reviewed Original ResearchConceptsMMP-12Pulmonary fibrosisWild typeGrowth factorInterstitial lung diseaseEffects of TGFMatrix metalloproteinase-12Pulmonary diseaseExaggerated productionPulmonary responseLung diseaseMMP-9Effector functionsTIMP-1Matrix metalloproteinaseFibrosisPotent stimulatorMetalloproteinase-12TGFBax activationInflammationPathogenesisBaxApoptosisDisease
2006
Transgenic Modeling of Transforming Growth Factor-β1
Lee CG, Kang HR, Homer RJ, Chupp G, Elias JA. Transgenic Modeling of Transforming Growth Factor-β1. Annals Of The American Thoracic Society 2006, 3: 418-423. PMID: 16799085, PMCID: PMC2658706, DOI: 10.1513/pats.200602-017aw.Peer-Reviewed Original ResearchConceptsTissue fibrosisMucus metaplasiaIL-13Alveolar remodelingSpecific chemokine receptorsTransforming Growth Factor-β1Vascular endothelial growth factorGrowth factor-β1Endothelial growth factorEosinophilic inflammationTh2 responsesVascular responsesChemokine receptorsCC chemokinesPathologic fibrosisMurine lungEpithelial apoptosisFactor-β1Transgenic miceFibrosisPotent stimulatorAdenosine metabolismIL-11Transgenic modelingInflammationAdenosine metabolism and murine strain–specific IL-4–induced inflammation, emphysema, and fibrosis
Ma B, Blackburn MR, Lee CG, Homer RJ, Liu W, Flavell RA, Boyden L, Lifton RP, Sun CX, Young HW, Elias JA. Adenosine metabolism and murine strain–specific IL-4–induced inflammation, emphysema, and fibrosis. Journal Of Clinical Investigation 2006, 116: 1274-1283. PMID: 16670768, PMCID: PMC1451205, DOI: 10.1172/jci26372.Peer-Reviewed Original ResearchConceptsIL-4C57BL/6 miceBALB/cAirway fibrosisEosinophilic inflammationAdenosine metabolismEmphysematous alveolar destructionTissue adenosine levelsAdenosine receptor expressionIL-4 inducesAdenosine deaminase activityAlveolar destructionTh1 cytokinesC57BL/6 animalsEmphysematous destructionAdenosine levelsReceptor expressionTg animalsMurine lungMetalloproteinase-2Alveolar remodelingTissue inhibitorFibrosisInflammationPremature death
2004
Idiopathic pulmonary fibrosis: new insights into pathogenesis
Noble PW, Homer RJ. Idiopathic pulmonary fibrosis: new insights into pathogenesis. Clinics In Chest Medicine 2004, 25: 749-758. PMID: 15564020, DOI: 10.1016/j.ccm.2004.04.003.Peer-Reviewed Original ResearchConceptsUsual interstitial pneumoniaInterstitial pneumoniaUncontrolled lung inflammationUnique pathologic featuresProgressive clinical courseAnti-inflammatory therapyIdiopathic pulmonary fibrosisLung inflammationClinical coursePathologic featuresPulmonary fibrosisCardinal manifestationsInflammatory responseNew therapiesFibroblast functionPneumoniaPathogenesisTherapyCurrent thoughtsRecent reviewBiopsyInflammationFibrosisIPFEarly Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis
Lee CG, Cho SJ, Kang MJ, Chapoval SP, Lee PJ, Noble PW, Yehualaeshet T, Lu B, Flavell RA, Milbrandt J, Homer RJ, Elias JA. Early Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis. Journal Of Experimental Medicine 2004, 200: 377-389. PMID: 15289506, PMCID: PMC2211975, DOI: 10.1084/jem.20040104.Peer-Reviewed Original ResearchConceptsVivo effector functionGrowth factor-β1Early growth response gene-1Pulmonary fibrosisSeptal rupturePulmonary disordersInterstitial diseaseEffector functionsFibrotic responseMurine lungTissue fibrosisEpithelial apoptosisFactor-β1Alveolar remodelingResponse gene-1FibrosisBioactive TGFTGFMyocyte hyperplasiaGrowth factorEarly growth response geneApoptosisLungPathogenesisGene 1
2002
Transgenic Overexpression of Interleukin (IL)-10 in the Lung Causes Mucus Metaplasia, Tissue Inflammation, and Airway Remodeling via IL-13-dependent and -independent Pathways*
Lee CG, Homer RJ, Cohn L, Link H, Jung S, Craft JE, Graham BS, Johnson TR, Elias JA. Transgenic Overexpression of Interleukin (IL)-10 in the Lung Causes Mucus Metaplasia, Tissue Inflammation, and Airway Remodeling via IL-13-dependent and -independent Pathways*. Journal Of Biological Chemistry 2002, 277: 35466-35474. PMID: 12107190, DOI: 10.1074/jbc.m206395200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceChloride ChannelsCloning, MolecularDNA PrimersFluorescent Antibody TechniqueGene Expression RegulationIn Situ HybridizationInflammationInterleukin-10Interleukin-13LungMiceMice, TransgenicMolecular Sequence DataMucoproteinsMucous MembranePhenotypePolymerase Chain ReactionReceptors, Interleukin-4STAT6 Transcription FactorTrans-ActivatorsConceptsMucus metaplasiaIL-10Tissue inflammationIL-13Tumor necrosis factor productionIL-13/ILLipopolysaccharide-induced inflammationNecrosis factor productionAirway fibrosisNeutrophil accumulationAirway remodelingSubepithelial fibrosisGob-5Levels of mRNAMetaplasiaInflammationTransgenic miceFibrosisSTAT-6Effector propertiesTransgenic overexpressionFactor productionMiceInterleukinMultiple mechanisms