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
2021
Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. Journal Of Clinical Investigation 2021, 131: e136542. PMID: 33393489, PMCID: PMC7773383, DOI: 10.1172/jci136542.Peer-Reviewed Original ResearchConceptsNetrin-1Lung fibrosisCell-specific knockout miceΑ1-adrenoreceptor blockadeIPF lung tissueNeuronal guidance proteinsNetrin-1 expressionExtracellular matrix accumulationAdrenergic processesAdrenoreceptor antagonismAdrenoreceptor blockadeFibrotic histologyInflammatory scarringIPF cohortAdrenergic nervesΑ1-blockersImproved survivalColorectal carcinomaLung tissueKnockout miceCollagen accumulationFibrosisMatrix accumulationMacrophagesGuidance proteins
2019
Shared and Tissue-Specific Expression Signatures between Bone Marrow from Primary Myelofibrosis and Essential Thrombocythemia
Ishikawa G, Fujiwara N, Hirschfield H, Varricchio L, Hoshida Y, Barosi G, Rosti V, Padilla M, Mazzarini M, Friedman SL, Hoffman R, Migliaccio AR. Shared and Tissue-Specific Expression Signatures between Bone Marrow from Primary Myelofibrosis and Essential Thrombocythemia. Experimental Hematology 2019, 79: 16-25.e3. PMID: 31678370, PMCID: PMC6910948, DOI: 10.1016/j.exphem.2019.10.001.Peer-Reviewed Original ResearchConceptsBone marrowLung fibrosisMyeloproliferative neoplasmsEssential thrombocytopeniaLiver fibrosisPhiladelphia-negative myeloproliferative neoplasmsProtein 1Possible therapeutic targetPrimary myelofibrosis patientsExpression of Id1Extracellular matrix protein 1Poor prognosisIL-8Myelofibrosis patientsEssential thrombocythemiaTherapeutic targetPrimary myelofibrosisFibrosisMegakaryocyte hyperplasiaCholesterol homeostasisBM functionHematopoietic failureMatrix protein 1K-rasPotential target