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 approaches
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 ResearchConceptsThyroid hormonesMitochondrial functionPulmonary fibrosisLung fibrosisLung epitheliumFibrosisMiceHormoneEpitheliumIdentification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis
Vukmirovic M, Herazo-Maya JD, Blackmon J, Skodric-Trifunovic V, Jovanovic D, Pavlovic S, Stojsic J, Zeljkovic V, Yan X, Homer R, Stefanovic B, Kaminski N. Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis. BMC Pulmonary Medicine 2017, 17: 15. PMID: 28081703, PMCID: PMC5228096, DOI: 10.1186/s12890-016-0356-4.Peer-Reviewed Original ResearchConceptsPaired-end sequencingTranscript profilingHuman genomeRNA sequencingTranscriptomic profilingFFPE lung tissuesSequencing readsLung tissueTotal RNABackgroundIdiopathic pulmonary fibrosisLethal lung diseaseSequencingReadsProfilingPulmonary fibrosisLung diseaseUnknown etiologyIPF tissueGenomeHiSeqTissueTopHat2GenesIPFRNA
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
Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis
Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCHI3L1 levelsChitinase 3Lungs of patientsAlternative macrophage activationLevel of apoptosisAcute exacerbationFibroproliferative repairLung transplantationDisease exacerbationInjury phaseAmbulatory patientsEpithelial injuryPulmonary fibrosisIPF populationLung fibrosisMacrophage accumulationCHI3L1 expressionFibrotic phaseDisease progressionProfibrotic roleFibroproliferative responseMacrophage activationMyofibroblast transformationProtective roleCD4+CD25+FoxP3+ Regulatory Tregs inhibit fibrocyte recruitment and fibrosis via suppression of FGF-9 production in the TGF-β1 exposed murine lung
Peng X, Moore MW, Peng H, Sun H, Gan Y, Homer RJ, Herzog EL. CD4+CD25+FoxP3+ Regulatory Tregs inhibit fibrocyte recruitment and fibrosis via suppression of FGF-9 production in the TGF-β1 exposed murine lung. Frontiers In Pharmacology 2014, 5: 80. PMID: 24904415, PMCID: PMC4032896, DOI: 10.3389/fphar.2014.00080.Peer-Reviewed Original ResearchTGF-β1Lung fibrosisDepletion of TregsRole of TregsRegulatory T cellsMurine lung fibrosisHuman TGF-β1 geneFibroblast growth factor 9TGF-β1 signalingTGF-β1 geneGrowth factor 9Model of fibrosisRegulatory TregTreg quantityCD25 antibodyDoxycycline-inducible overexpressionPulmonary fibrosisNaïve CD4Fibrocyte recruitmentIL-1αFGF-9 expressionLung parenchymaT cellsTregsFibrocyte accumulationPulmonary 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
Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis
Reilkoff RA, Peng H, Murray LA, Peng X, Russell T, Montgomery R, Feghali-Bostwick C, Shaw A, Homer RJ, Gulati M, Mathur A, Elias JA, Herzog EL. Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2012, 187: 180-188. PMID: 23220917, PMCID: PMC3570653, DOI: 10.1164/rccm.201206-1109oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisRegulatory T cellsProgressive idiopathic pulmonary fibrosisSEMA 7ATGF-β1Pulmonary fibrosisLung fibrosisT cellsMurine lungIL-10Bone marrow-derived cellsAdoptive transfer approachT-cell mediatorsMarrow-derived cellsTransforming Growth Factor-β1Murine lung fibrosisGrowth factor-β1Lung CD4Adoptive transferIL-17AIL-4Disease progressionSemaphorin 7ACD4Mouse modelChronic 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 modelingPatientsTGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P
Murray LA, Chen Q, Kramer MS, Hesson DP, Argentieri RL, Peng X, Gulati M, Homer RJ, Russell T, van Rooijen N, Elias JA, Hogaboam CM, Herzog EL. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. The International Journal Of Biochemistry & Cell Biology 2010, 43: 154-162. PMID: 21044893, DOI: 10.1016/j.biocel.2010.10.013.Peer-Reviewed Original ResearchConceptsSerum amyloid PAnti-fibrotic effectsLung fibrosisFibrocyte accumulationAmyloid PAberrant extracellular matrix (ECM) depositionTransgenic mouse modelM2 macrophage differentiationPleiotropic growth factorExtracellular matrix depositionAirway inflammationIPF patientsAirway remodelingPulmonary fibrosisMacrophage accumulationLung diseaseLiposomal clodronateCXCL10 expressionM2 macrophagesMonocyte responsePulmonary macrophagesMouse modelCollagen depositionPathogenic mechanismsDisease severityInhibition 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
State of the Art. Mechanistic Heterogeneity in Chronic Obstructive Pulmonary Disease
Elias JA, Kang MJ, Crothers K, Homer R, Lee CG. State of the Art. Mechanistic Heterogeneity in Chronic Obstructive Pulmonary Disease. Annals Of The American Thoracic Society 2006, 3: 494-498. PMID: 16921126, DOI: 10.1513/pats.200603-068ms.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseVascular endothelial growth factorSecretory leukocyte proteinase inhibitorTh1/Tc1Obstructive pulmonary diseaseAlveolar destructionIFN-gammaMatrix metalloproteinasesMucus metaplasiaPulmonary diseaseCCR5-dependent mechanismEmphysematous alveolar destructionCigarette smoke exposureCytokine IFN-gammaIFN-gamma responsesEndothelial growth factorApoptosis-independent pathwayCCR5/Pulmonary fibrosisPulmonary responseSmoke exposureIL-13CC chemokinesFibrotic responseMurine lung