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 ResearchMeSH KeywordsAnimalsAutophagyBleomycinHomeostasisHumansIdiopathic Pulmonary FibrosisMacrophagesMiceMicroRNAsMitochondriaConceptsIdiopathic 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 ResearchMeSH KeywordsAdrenergic AgentsAnimalsBleomycinDNA, MitochondrialFibroblastsHumansIdiopathic Pulmonary FibrosisLungMiceSignal TransductionConceptsAdrenergic 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
2022
An Acute Exacerbation of Idiopathic Pulmonary Fibrosis After BNT162b2 mRNA COVID-19 Vaccination A Case Report
Ghincea A, Ryu C, Herzog EL. An Acute Exacerbation of Idiopathic Pulmonary Fibrosis After BNT162b2 mRNA COVID-19 Vaccination A Case Report. CHEST Journal 2022, 161: e71-e73. PMID: 35131075, PMCID: PMC8814523, DOI: 10.1016/j.chest.2021.07.2160.Peer-Reviewed Case Reports and Technical NotesConceptsIdiopathic pulmonary fibrosisAE-IPFAcute exacerbationPulmonary fibrosisLung diseaseCase reportFatal interstitial lung diseaseMRNA COVID-19 vaccinationChronic lung diseaseInterstitial lung diseaseVaccine-preventable diseasesNovel case reportA Case ReportCOVID-19 vaccinationScar tissue formationRespiratory decompensationAdverse eventsPulmonary embolismVulnerable patientsDrug toxicityPotential associationShort courseDiseaseExacerbationFibrosis
2020
Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of idiopathic pulmonary fibrosis
Sakamoto K, Furukawa T, Yamano Y, Kataoka K, Teramachi R, Walia A, Suzuki A, Inoue M, Nakahara Y, Ryu C, Hashimoto N, Kondoh Y. Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of idiopathic pulmonary fibrosis. European Respiratory Journal 2020, 57: 2001346. PMID: 32855220, PMCID: PMC8177039, DOI: 10.1183/13993003.01346-2020.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAcute exacerbationPulmonary fibrosisDisease progressionFatal interstitial lung diseaseInterstitial lung diseaseSerum mitochondrial DNAAccepted biomarkersClinical deteriorationMedian survivalDeadly complicationDisease courseLethal complicationLung functionLung diseaseUnknown etiologyExacerbationUnmet needProgressionComplicationsRapid deteriorationPatientsFibrosisDevastating diseaseDiseaseReduced Sialylation and Bioactivity of the Antifibrotic Protein Serum Amyloid P in the Sera of Patients with Idiopathic Pulmonary Fibrosis
Chen W, Karhadkar TR, Ryu C, Herzog EL, Gomer RH. Reduced Sialylation and Bioactivity of the Antifibrotic Protein Serum Amyloid P in the Sera of Patients with Idiopathic Pulmonary Fibrosis. ImmunoHorizons 2020, 4: 352-362. PMID: 32576593, PMCID: PMC8500545, DOI: 10.4049/immunohorizons.2000043.Peer-Reviewed Original ResearchConceptsSerum amyloid PIPF patientsPulmonary fibrosisFibrocyte differentiationIL-10 accumulationAmyloid PEffects of SAPIdiopathic pulmonary fibrosis (IPF) pathogenesisPulmonary fibrosis pathogenesisIdiopathic pulmonary fibrosisBronchoalveolar lavage fluidSera of patientsHigh extracellular levelsPotential therapeutic targetDifferentiation of monocytesSialic acidIPF pathogenesisIL-10Scar-like tissueLavage fluidHealthy controlsFatal disorderFibrosis pathogenesisHuman PBMCsTherapeutic target
2019
GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis
Zhang Y, Jiang M, Nouraie M, Roth MG, Tabib T, Winters S, Chen X, Sembrat J, Chu Y, Cardenes N, Tuder RM, Herzog EL, Ryu C, Rojas M, Lafyatis R, Gibson KF, McDyer JF, Kass DJ, Alder JK. GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2019, 317: l510-l521. PMID: 31432710, PMCID: PMC6842909, DOI: 10.1152/ajplung.00062.2019.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlveolar Epithelial CellsAnimalsBleomycinBronchoalveolar Lavage FluidCase-Control StudiesDisease Models, AnimalFemaleGene Expression ProfilingGrowth Differentiation Factor 15HumansIdiopathic Pulmonary FibrosisLungMaleMiceMiddle AgedRespiratory Function TestsSeverity of Illness IndexSurvival AnalysisTelomereTranscriptomeConceptsIdiopathic pulmonary fibrosisBleomycin challengePulmonary fibrosisEpithelial cellsDisease pathologyConcentrations of GDF15Type II alveolar epithelial cellsInterstitial lung diseaseDifferentiation factor 15Multiple independent cohortsAlveolar epithelial cellsLung epithelial cellsIPF patientsPulmonary functionBronchoalveolar lavagePoor outcomeLung diseasePeripheral bloodEpithelial dysfunctionTelomere dysfunctionLung tissueFactor 15Epithelial stressIndependent cohortUseful biomarkerNew Applications of Old Drugs as Novel Therapies in Idiopathic Pulmonary Fibrosis. Metformin, Hydroxychloroquine, and Thyroid Hormone
Manning EP, Losier A, Emeagwali N, Ryu C, Honiden S. New Applications of Old Drugs as Novel Therapies in Idiopathic Pulmonary Fibrosis. Metformin, Hydroxychloroquine, and Thyroid Hormone. American Journal Of Respiratory And Critical Care Medicine 2019, 199: 1561-1563. PMID: 30822095, PMCID: PMC7051474, DOI: 10.1164/rccm.201809-1700rr.Peer-Reviewed Original ResearchMeSH KeywordsBleomycinHumansHydroxychloroquineIdiopathic Pulmonary FibrosisMetforminThyroid Hormones
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
2016
Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis
Tzouvelekis A, Herazo‐Maya J, Slade M, Chu J, Deiuliis G, Ryu C, Li Q, Sakamoto K, Ibarra G, Pan H, Gulati M, Antin‐Ozerkis D, Herzog EL, Kaminski N. Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis. Respirology 2016, 22: 486-493. PMID: 27761978, PMCID: PMC5352520, DOI: 10.1111/resp.12920.Peer-Reviewed Original ResearchConceptsTransplant-free survivalIdiopathic pulmonary fibrosisMMP-7 concentrationsMatrix metalloproteinase-7IPF patientsCause mortalityPulmonary fibrosisHealthy controlsMultivariate Cox proportional hazards modelCox proportional hazards modelPulmonary function parametersVariable clinical courseBaseline pulmonary function parametersProportional hazards modelIPF biomarkersProgressive diseaseClinical coursePoor prognosisPrognostic valueVital capacityIndependent biomarkerLung capacityPrognostic thresholdPlasma concentrationsMortality riskThe Airway in Idiopathic Pulmonary Fibrosis: Protecting the Lung or Promoting Disease?
Ryu C, Homer RJ, Herzog EL. The Airway in Idiopathic Pulmonary Fibrosis: Protecting the Lung or Promoting Disease? American Journal Of Respiratory And Critical Care Medicine 2016, 193: 1081-1082. PMID: 27174477, PMCID: PMC4872674, DOI: 10.1164/rccm.201601-0055ed.Peer-Reviewed Original Research