2022
CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging.
Cui H, Xie N, Banerjee S, Dey T, Liu RM, Antony VB, Sanders YY, Adams TS, Gomez JL, Thannickal VJ, Kaminski N, Liu G. CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 459-475. PMID: 35687485, DOI: 10.1164/rccm.202109-2151oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung fibrosisCD38 expressionAlveolar epithelial cell injuryEpithelial cell injuryEffective therapeutic strategyHuman lung parenchymaIPF lungsLung functionPulmonary fibrosisDisease progressionFibrotic lungsReal-time PCRYoung miceLung parenchymaOld miceCell injuryTherapeutic strategiesFibrosisPharmacological inactivationCD38Single-cell RNA sequencingFlow cytometryWestern blottingOld animalsCharacterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
2021
Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis
Kumar A, Elko E, Bruno SR, Mark ZF, Chamberlain N, Mihavics BK, Chandrasekaran R, Walzer J, Ruban M, Gold C, Lam YW, Ghandikota S, Jegga AG, Gomez JL, Janssen-Heininger YM, Anathy V. Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis. Thorax 2021, 77: 669-678. PMID: 34400514, PMCID: PMC8847543, DOI: 10.1136/thoraxjnl-2021-216882.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisProtein disulfide isomerase A3Lung fibrosisPulmonary fibrosisClub cellsFibrosis-related proteinsMechanism of actionControl patientsLung functionBleomycin modelLung parenchymaFibrosisTherapeutic potentialMiceOsteopontin productionSpecific deletionPatientsProtein signaturesInhibitionResearch ConsortiumPathologyCellsSPP1Human transcriptome datasetsMajor interactorsMicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease
Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan IS, Li CX, Sköld C, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra RS, Wheelock ÅM, Gomez JL, Kaminski N, Lee PJ, Sauler M. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease. JCI Insight 2021, 6: e134218. PMID: 33290275, PMCID: PMC7934877, DOI: 10.1172/jci.insight.134218.Peer-Reviewed Original ResearchConceptsCellular stress responseStress responseHomology-directed DNA repairDNA damage responseProtein BRCA1Damage responseCellular stressDNA repairProtein BimCOPD lung tissueLung epithelial cellsCellular responsesExpression arraysEpithelial cell apoptosisDNA damageChronic obstructive pulmonary diseaseBRCA1 expressionCell apoptosisApoptosisEpithelial cellsCritical mechanismMicroRNAsRegulatorObstructive pulmonary diseaseIncreases SusceptibilityMacrophage-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
2020
An endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis
Korde A, Ahangari F, Haslip M, Zhang X, Liu Q, Cohn L, Gomez JL, Chupp G, Pober JS, Gonzalez A, Takyar SS. An endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis. Journal Of Allergy And Clinical Immunology 2020, 145: 550-562. PMID: 32035607, PMCID: PMC8440091, DOI: 10.1016/j.jaci.2019.10.031.Peer-Reviewed Original ResearchConceptsMiR-1 levelsAllergic airway inflammationChronic rhinosinusitisP-selectin levelsEndothelium-specific overexpressionLung endotheliumAirway eosinophiliaAirway inflammationAsthmatic patientsTissue eosinophiliaMiR-1House dust mite modelEndothelial cellsThymic stromal lymphopoietinNumber of hospitalizationsHuman lung endotheliumIL-13 stimulationCRS cohortQuantitative RT-PCRSputum eosinophiliaAirway obstructionAsthma modelAsthma phenotypesLentiviral vector deliveryMurine model
2018
Reducing protein oxidation reverses lung fibrosis
Anathy V, Lahue KG, Chapman DG, Chia SB, Casey DT, Aboushousha R, van der Velden JLJ, Elko E, Hoffman SM, McMillan DH, Jones JT, Nolin JD, Abdalla S, Schneider R, Seward DJ, Roberson EC, Liptak MD, Cousins ME, Butnor KJ, Taatjes DJ, Budd RC, Irvin CG, Ho YS, Hakem R, Brown KK, Matsui R, Bachschmid MM, Gomez JL, Kaminski N, van der Vliet A, Janssen-Heininger YMW. Reducing protein oxidation reverses lung fibrosis. Nature Medicine 2018, 24: 1128-1135. PMID: 29988126, PMCID: PMC6204256, DOI: 10.1038/s41591-018-0090-y.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisLung fibrosisDirect administrationAirways of miceGrowth factor beta 1Transgenic mouse modelFibrotic lungsLung tissueMouse modelAged animalsFibrosisLung epitheliumTherapeutic potentialExcessive depositionBeta 1Transgenic overexpressionOxidative stressExact mechanismAirwayGlrxLungMiceAdministrationOxidative mechanisms