2023
α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis
Ishikawa G, Peng X, McGovern J, Woo S, Perry C, Liu A, Yu S, Ghincea A, Kishchanka A, Fiorini V, Hu B, Sun Y, Sun H, Ryu C, Herzog E. α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2023, 324: l639-l651. PMID: 36648147, PMCID: PMC10110730, DOI: 10.1152/ajplung.00119.2022.Peer-Reviewed Original ResearchConceptsAdrenergic nerve supplyIdiopathic pulmonary fibrosisΑ1 adrenoreceptorsPulmonary fibrosisNerve supplyCultured normal human lung fibroblastsInnate immune ligandsLung fibrosis modelNormal human lung fibroblastsSmooth muscle actinHuman lung fibroblastsAdrenal resectionAdrenoreceptor antagonismExtracellular mtDNAIPF cohortImproved survivalΑ1-adrenoreceptor antagonistsLung fibrosisAdrenal sourceFibroblast accumulationAdrenoreceptor antagonistBleomycin modelFibrosis modelLung fibrogenesisMouse model
2017
Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis
Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G. Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1571-1581. PMID: 28783377, PMCID: PMC5754440, DOI: 10.1164/rccm.201612-2480oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedDisease-Free SurvivalDNA, MitochondrialFemaleFibroblastsHumansIdiopathic Pulmonary FibrosisMaleConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsExtracellular mitochondrial DNABronchoalveolar lavageIPF fibroblastsPulmonary fibrosisInnate immune ligandsEvent-free survivalSmooth muscle actin expressionMtDNA concentrationsSmooth muscle actin-expressing myofibroblastsGrowth factor-β1Muscle actin expressionHuman lung fibroblastsTGF-β1 stimulationExtracellular mtDNAIPF cohortClinical outcomesControl subjectsDisease progressionGlycolytic reprogrammingSoluble mediatorsTGF-β1Factor-β1Immune ligands
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 role
2013
Fibroblast engraftment in the decellularized mouse lung occurs via a β1-integrin-dependent, FAK-dependent pathway that is mediated by ERK and opposed by AKT
Sun H, Calle E, Chen X, Mathur A, Zhu Y, Mendez J, Zhao L, Niklason L, Peng X, Peng H, Herzog EL. Fibroblast engraftment in the decellularized mouse lung occurs via a β1-integrin-dependent, FAK-dependent pathway that is mediated by ERK and opposed by AKT. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2013, 306: l463-l475. PMID: 24337923, PMCID: PMC3949086, DOI: 10.1152/ajplung.00100.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingBioartificial OrgansCell AdhesionCell LineCell ProliferationCell SurvivalExtracellular Signal-Regulated MAP KinasesFibroblastsFocal Adhesion Kinase 1Integrin beta1LungMicePhosphorylationProto-Oncogene Proteins c-aktRatsRho-Associated KinasesTissue EngineeringTissue ScaffoldsConceptsExtracellular signal-regulated kinase (ERK) inhibitorSignal-regulated kinase inhibitorKinase inhibitorsERK-dependent mannerFAK-dependent pathwayFocal adhesion kinase (FAK) inhibitorFibroblast cell lineMouse fibroblast cell lineTissue-engineered lungsMinimal cell deathCell survivalCell deathMouse lungAkt inhibitorMouse fibroblastsProteinaceous componentsMammalian lungCell proliferationCell linesNumber of mechanismsAktTime-dependent increaseLung scaffoldsCell numberCell density