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
2019
GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance
Luan HH, Wang A, Hilliard B, Carvalho F, Rosen CE, Ahasic A, Herzog E, Kang I, Pisani MA, Yu S, Zhang C, Ring A, Young L, Medzhitov R. GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance. Cell 2019, 178: 1231-1244.e11. PMID: 31402172, PMCID: PMC6863354, DOI: 10.1016/j.cell.2019.07.033.Peer-Reviewed Original ResearchConceptsViral infectionTriglyceride metabolismImpaired cardiac functionRole of GDF15Differentiation factor 15Plasma triglyceride levelsSympathetic outflowInflammatory damageTriglyceride levelsCardiac functionInflammatory responseExogenous administrationProtective effectFactor 15GDF15Central mediatorTissue toleranceBody temperatureInfectionMetabolismSepsisInflammationAdministrationHormone
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
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
2010
TGF-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 severity
2004
Lack of a Fusion Requirement for Development of Bone Marrow-Derived Epithelia
Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS. Lack of a Fusion Requirement for Development of Bone Marrow-Derived Epithelia. Science 2004, 305: 90-93. PMID: 15232107, DOI: 10.1126/science.1098925.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta-GalactosidaseBone Marrow CellsBone Marrow TransplantationCell DifferentiationCell FusionCobra Cardiotoxin ProteinsElapid VenomsEpithelial CellsFemaleGreen Fluorescent ProteinsHepatocytesKeratinocytesKeratinsLuminescent ProteinsMaleMiceMice, TransgenicMuscle CellsRadiation, IonizingRecombinasesRecombination, GeneticReverse Transcriptase Polymerase Chain ReactionStem CellsX ChromosomeY ChromosomeConceptsCell-cell fusionBone marrow-derived cellsCre/lox systemGreen fluorescent protein expressionFluorescent protein expressionEpithelial cellsDevelopmental plasticityLox systemCell fusionProtein expressionMarrow-derived cellsTransgenic miceCellsBone marrowFusionFusion requirementsPlasticityExpression