2023
microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mouseα1 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
Antifibrotic role of vascular endothelial growth factor in pulmonary fibrosis
Murray LA, Habiel DM, Hohmann M, Camelo A, Shang H, Zhou Y, Coelho AL, Peng X, Gulati M, Crestani B, Sleeman MA, Mustelin T, Moore MW, Ryu C, Osafo-Addo AD, Elias JA, Lee CG, Hu B, Herazo-Maya JD, Knight DA, Hogaboam CM, Herzog EL. Antifibrotic role of vascular endothelial growth factor in pulmonary fibrosis. JCI Insight 2017, 2: e92192. PMID: 28814671, PMCID: PMC5621899, DOI: 10.1172/jci.insight.92192.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisPulmonary fibrosisEndothelial cell-derived mediatorsThrombospondin-1Chronic progressive declineIntratracheal bleomycin challengeVEGF transgenic miceCell-derived mediatorsLung-specific overexpressionVascular endothelial growth factorEpithelial cell injuryLevels of VEGFAssociation of VEGFEndothelial growth factorImpaired restitutionBleomycin challengeIPF pathogenesisLung functionEpithelial wound closureLung fibrosisAntifibrotic roleHealthy controlsPreclinical modelsProgressive phenotypeCell injury
2016
Plexin 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