2022
Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactionsLung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis.
De Sadeleer LJ, McDonough JE, Schupp JC, Yan X, Vanstapel A, Van Herck A, Everaerts S, Geudens V, Sacreas A, Goos T, Aelbrecht C, Nawrot TS, Martens DS, Schols D, Claes S, Verschakelen JA, Verbeken EK, Ackermann M, Decottignies A, Mahieu M, Hackett TL, Hogg JC, Vanaudenaerde BM, Verleden SE, Kaminski N, Wuyts WA. Lung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2022, 205: 60-74. PMID: 34724391, PMCID: PMC8865586, DOI: 10.1164/rccm.202103-0569oc.Peer-Reviewed Original ResearchConceptsFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisHypersensitivity pneumonitisLung zonesMolecular traitsUnused donor lungsInterstitial lung diseaseLocal disease extentProgression of fibrosisSevere fibrosis groupGene co-expression network analysisCo-expression network analysisExplant lungsDonor lungsLung involvementEndothelial functionLung findingsDisease extentPulmonary fibrosisLung diseaseFibrosis groupLung microenvironmentClinical behaviorDisease progressionBAL samples
2021
Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets
Reichmann MT, Tezera LB, Vallejo AF, Vukmirovic M, Xiao R, Reynolds J, Jogai S, Wilson S, Marshall B, Jones MG, Leslie A, D'Armiento JM, Kaminski N, Polak ME, Elkington P. Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets. Journal Of Clinical Investigation 2021, 131 PMID: 34128839, PMCID: PMC8321576, DOI: 10.1172/jci148136.Peer-Reviewed Original ResearchConceptsTherapeutic targetTB granulomasHuman TB diseaseHuman tuberculosis granulomasNoninfectious granulomatous diseasesPathological host responsesSarcoidosis lymph nodesInflammatory immune responseSphingosine kinase 1 inhibitionInflammatory mediator secretionPotential therapeutic targetHuman TB granulomasKinase 1 inhibitionHuman cell culture modelsInfected granulomasTB diseaseLymph nodesTB outcomesTuberculosis granulomasStandard treatmentSphingosine kinase 1Granulomatous diseaseLaser capture microdissectionMediator secretionExtensive infectionBlood Transcriptomics Predicts Progression of Pulmonary Fibrosis and Associated Natural Killer Cells.
Huang Y, Oldham JM, Ma SF, Unterman A, Liao SY, Barros AJ, Bonham CA, Kim JS, Vij R, Adegunsoye A, Strek ME, Molyneaux PL, Maher TM, Herazo-Maya JD, Kaminski N, Moore BB, Martinez FJ, Noth I. Blood Transcriptomics Predicts Progression of Pulmonary Fibrosis and Associated Natural Killer Cells. American Journal Of Respiratory And Critical Care Medicine 2021, 204: 197-208. PMID: 33689671, PMCID: PMC8650792, DOI: 10.1164/rccm.202008-3093oc.Peer-Reviewed Original ResearchFibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis
Nakahara Y, Hashimoto N, Sakamoto K, Enomoto A, Adams TS, Yokoi T, Omote N, Poli S, Ando A, Wakahara K, Suzuki A, Inoue M, Hara A, Mizutani Y, Imaizumi K, Kawabe T, Rosas IO, Takahashi M, Kaminski N, Hasegawa Y. Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis. European Respiratory Journal 2021, 58: 2003397. PMID: 34049947, DOI: 10.1183/13993003.03397-2020.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisAnti-fibrotic propertiesRole of fibroblastsFibroblastic fociPathogenesis of IPFLung fibrosis modelSenescence-associated secretory phenotypeNormal lung samplesMesenchymal stromal cellsIPF patientsIPF lungsDense fibrosisPathological hallmark lesionsFibrosis modelFibrotic lungsHallmark lesionsSingle-cell atlasActive fibrogenesisElderly individualsLung samplesFibrosisSingle-cell RNA sequencingFibrotic regionsSecretory phenotypeMicroRNA 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 SusceptibilityElevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers
Zhang Y, Tedrow J, Nouraie M, Li X, Chandra D, Bon J, Kass DJ, Fuhrman CR, Leader JK, Duncan SR, Kaminski N, Sciurba FC. Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers. Thorax 2021, 76: 335-342. PMID: 33479043, PMCID: PMC8249179, DOI: 10.1136/thoraxjnl-2020-215356.Peer-Reviewed Original ResearchConceptsAirflow obstructionPlasma levelsLung tissueEmphysema severitySmoking-related lung diseaseAssociation of lungExpiratory airflow obstructionFormer tobacco smokersLevels of PTX3PTX3 gene expressionElevated plasma levelsHyaluronic acid levelsBlood of subjectsPlasma PTX3PTX3 levelsLung functionTobacco exposureClinical outcomesTobacco smokersLung diseasePentraxin 3Predictive biomarkersPTX3 expressionLower riskDisease patterns
2020
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytesTocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes
Price CC, Altice FL, Shyr Y, Koff A, Pischel L, Goshua G, Azar MM, Mcmanus D, Chen SC, Gleeson SE, Britto CJ, Azmy V, Kaman K, Gaston DC, Davis M, Burrello T, Harris Z, Villanueva MS, Aoun-Barakat L, Kang I, Seropian S, Chupp G, Bucala R, Kaminski N, Lee AI, LoRusso PM, Topal JE, Dela Cruz C, Malinis M. Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes. CHEST Journal 2020, 158: 1397-1408. PMID: 32553536, PMCID: PMC7831876, DOI: 10.1016/j.chest.2020.06.006.Peer-Reviewed Original ResearchConceptsCytokine release syndromeTocilizumab-treated patientsSevere diseaseRelease syndromeTocilizumab treatmentInflammatory biomarkersNonsevere diseaseSoluble IL-2 receptor levelsHigh-sensitivity C-reactive proteinIL-2 receptor levelsConsecutive COVID-19 patientsIL-6 receptor antagonistMechanical ventilation outcomesC-reactive proteinCOVID-19 patientsHigher admission levelsRace/ethnicityMV daysVentilation outcomesAdverse eventsChart reviewClinical responseMedian ageWhite patientsClinical outcomesGenome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis
Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, Kraven LM, Obeidat M, Li X, Ng M, Braybrooke R, Molina-Molina M, Hobbs BD, Putman RK, Sakornsakolpat P, Booth HL, Fahy WA, Hart SP, Hill MR, Hirani N, Hubbard RB, McAnulty RJ, Millar AB, Navaratnam V, Oballa E, Parfrey H, Saini G, Whyte MKB, Zhang Y, Kaminski N, Adegunsoye A, Strek ME, Neighbors M, Sheng XR, Gudmundsson G, Gudnason V, Hatabu H, Lederer DJ, Manichaikul A, Newell JD, O’Connor G, Ortega VE, Xu H, Fingerlin TE, Bossé Y, Hao K, Joubert P, Nickle DC, Sin DD, Timens W, Furniss D, Morris AP, Zondervan KT, Hall IP, Sayers I, Tobin MD, Maher TM, Cho MH, Hunninghake GM, Schwartz DA, Yaspan BL, Molyneaux PL, Flores C, Noth I, Jenkins RG, Wain LV. Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 201: 564-574. PMID: 31710517, PMCID: PMC7047454, DOI: 10.1164/rccm.201905-1017oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedCase-Control StudiesCell Cycle ProteinsFemaleGene ExpressionGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIdiopathic Pulmonary FibrosisIntracellular Signaling Peptides and ProteinsKinesinsMaleMiddle AgedRisk AssessmentSignal TransductionSpindle ApparatusTOR Serine-Threonine KinasesConceptsGenome-wide association studiesAssociation studiesIPF susceptibilityNew genome-wide significant signalsGenome-wide significant signalsGenome-wide analysisCell-cell adhesionLarge genome-wide association studiesImportance of mTORPolygenic risk score analysisTelomere maintenanceCausal genesFunctional analysisSusceptibility variantsRisk score analysisMultiple pathwaysGenetic associationGenesHost defensePolygenic risk scoresIndependent studiesPossible roleExpression associatesSignificant signalRecent studies
2019
Transcriptional regulatory model of fibrosis progression in the human lung
McDonough JE, Ahangari F, Li Q, Jain S, Verleden SE, Herazo-Maya J, Vukmirovic M, DeIuliis G, Tzouvelekis A, Tanabe N, Chu F, Yan X, Verschakelen J, Homer RJ, Manatakis DV, Zhang J, Ding J, Maes K, De Sadeleer L, Vos R, Neyrinck A, Benos PV, Bar-Joseph Z, Tantin D, Hogg JC, Vanaudenaerde BM, Wuyts WA, Kaminski N. Transcriptional regulatory model of fibrosis progression in the human lung. JCI Insight 2019, 4 PMID: 31600171, PMCID: PMC6948862, DOI: 10.1172/jci.insight.131597.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAdvanced fibrosisAlveolar surface densityFibrosis progressionLung fibrosisHuman lungDynamic Regulatory Events MinerExtent of fibrosisIPF lungsPulmonary fibrosisControl lungsIPF tissueB lymphocytesFibrosisLungLinear mixed-effects modelsMixed-effects modelsGene expression changesSystems biology modelsDifferential gene expression analysisGene expression analysisProgressionGene expression networksRNA sequencingBiology modelsPlasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
Ryu C, Brandsdorfer C, Adams T, Hu B, Kelleher DW, Yaggi M, Manning EP, Walia A, Reeves B, Pan H, Winkler J, Minasyan M, Dela Cruz CS, Kaminski N, Gulati M, Herzog EL. Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis. European Respiratory Journal 2019, 54: 1801762. PMID: 31273041, PMCID: PMC8088542, DOI: 10.1183/13993003.01762-2018.Peer-Reviewed Original ResearchConceptsExtrapulmonary diseaseMitochondrial DNAExtracellular mtDNABAL fluidAlpha-1 antitrypsin deficiencyPlasma mitochondrial DNAPlasma of patientsAfrican AmericansExtrapulmonary sarcoidosisSarcoidosis cohortSarcoidosis subjectsScadding stageAfrican American descentClinical featuresClinical findingsGranulomatous diseaseHealthy controlsAntitrypsin deficiencyGenomic researchHigher oddsSarcoidosisAggressive phenotypeMechanistic basisDiseaseTherapeutic insightsSialylation of MUC4β N-glycans by ST6GAL1 orchestrates human airway epithelial cell differentiation associated with Type-2 inflammation
Zhou X, Kinlough CL, Hughey RP, Jin M, Inoue H, Etling E, Modena BD, Kaminski N, Bleecker ER, Meyers DA, Jarjour NN, Trudeau JB, Holguin F, Ray A, Wenzel SE. Sialylation of MUC4β N-glycans by ST6GAL1 orchestrates human airway epithelial cell differentiation associated with Type-2 inflammation. JCI Insight 2019, 4 PMID: 30730306, PMCID: PMC6483602, DOI: 10.1172/jci.insight.122475.Peer-Reviewed Original ResearchConceptsHuman airway epithelial cellsEpithelial dysfunctionPrimary human airway epithelial cellsAirway epithelial cell differentiationT2-high asthmaType 2 inflammationAirway epithelial cellsGoblet cell differentiationEpithelial cell proliferationAirway specimensT2 biomarkersAsthmatic patientsSputum supernatantsT2 inflammationIL-13Cell differentiationAsthmaEpithelial cell differentiationSpecific mucinsEpithelial cell fateΒ-galactoside αEpithelial glycoproteinEpithelial cellsPotential targetEpithelial differentiationBAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis
Prasse A, Binder H, Schupp JC, Kayser G, Bargagli E, Jaeger B, Hess M, Rittinghausen S, Vuga L, Lynn H, Violette S, Jung B, Quast K, Vanaudenaerde B, Xu Y, Hohlfeld JM, Krug N, Herazo-Maya JD, Rottoli P, Wuyts WA, Kaminski N. BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2019, 199: 622-630. PMID: 30141961, PMCID: PMC6396865, DOI: 10.1164/rccm.201712-2551oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway basal cellsChronic obstructive pulmonary diseaseObstructive pulmonary diseasePulmonary diseaseBAL cellsBasal cellsPulmonary fibrosisControl subjectsCell gene expressionIndependent IPF cohortsNine-gene signatureIPF cohortDerivation cohortClinical parametersRetrospective studyUnivariate analysisUnpredictable courseCell involvementDiscovery cohortGene expressionHealthy volunteersCox modelStage IIIFatal diseaseAssessing Patterns of Palliative Care Referral and Location of Death in Patients with Idiopathic Pulmonary Fibrosis: A Sixteen-Year Single-Center Retrospective Cohort Study
Zou RH, Nouraie M, Chen X, Saul MI, Kaminski N, Gibson KF, Kass DJ, Lindell KO. Assessing Patterns of Palliative Care Referral and Location of Death in Patients with Idiopathic Pulmonary Fibrosis: A Sixteen-Year Single-Center Retrospective Cohort Study. Journal Of Palliative Medicine 2019, 22: 538-544. PMID: 30615545, PMCID: PMC7869870, DOI: 10.1089/jpm.2018.0400.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisSpecialty referral centerIPF patientsPalliative careLocation of deathPC referralHospice deathsReferral centerPulmonary fibrosisLife discussionsCenter retrospective cohort studyPalliative care referralTotal outpatient visitsCharlson Comorbidity IndexRetrospective cohort studyFatal lung diseasePatient-provider relationshipComorbidity indexHospital deathSevere comorbiditiesTransplant recipientsCare referralCohort studyMedian survivalClinical factors
2018
Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis
McDonough JE, Kaminski N, Thienpont B, Hogg JC, Vanaudenaerde BM, Wuyts WA. Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis. Thorax 2018, 74: 132. PMID: 30366970, PMCID: PMC6467239, DOI: 10.1136/thoraxjnl-2018-211929.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung functionPulmonary fibrosisExtensive pathological changesSevere lung diseaseLung Tissue Research ConsortiumCorrelation network analysisIPF cohortIPF groupLung diseaseControl subjectsUpregulated modulesT cellsImmune responsePathological changesLeucocyte activationB cellsClinical relevanceSurfactant metabolismDisease pathologyInterferon responseFibrosisBlood vesselsPathological processesGene correlation network analysisCharacteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease – analysis of institutional and population data
Yoon JH, Nouraie M, Chen X, Zou RH, Sellares J, Veraldi KL, Chiarchiaro J, Lindell K, Wilson DO, Kaminski N, Burns T, Trejo Bittar H, Yousem S, Gibson K, Kass DJ. Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease – analysis of institutional and population data. Respiratory Research 2018, 19: 195. PMID: 30285867, PMCID: PMC6171146, DOI: 10.1186/s12931-018-0899-4.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisSingle lung transplantInterstitial lung diseaseLung cancerIPF patientsPulmonary fibrosisIPF ILDNon-IPF ILD patientsLung Cancer RegistrySquamous cell histologySquamous cell carcinomaStandard incidence ratioBackgroundLung cancerCenter registryILD patientsLung transplantCell histologyClinical characteristicsInterstitial lungCancer RegistryIncidence ratiosWorse prognosisLower lobeCell carcinomaLung diseasePD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production
Celada LJ, Kropski JA, Herazo-Maya JD, Luo W, Creecy A, Abad AT, Chioma OS, Lee G, Hassell NE, Shaginurova GI, Wang Y, Johnson JE, Kerrigan A, Mason WR, Baughman RP, Ayers GD, Bernard GR, Culver DA, Montgomery CG, Maher TM, Molyneaux PL, Noth I, Mutsaers SE, Prele CM, Peebles R, Newcomb DC, Kaminski N, Blackwell TS, Van Kaer L, Drake WP. PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Science Translational Medicine 2018, 10 PMID: 30257954, PMCID: PMC6263177, DOI: 10.1126/scitranslmed.aar8356.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsBleomycinCD4-Positive T-LymphocytesCell ProliferationCollagen Type IDisease Models, AnimalFemaleFibroblastsGene Expression RegulationHumansIdiopathic Pulmonary FibrosisInterleukin-17MaleMiceMiddle AgedProgrammed Cell Death 1 ReceptorRNA, MessengerSarcoidosisSTAT3 Transcription FactorTh17 CellsTransforming Growth Factor beta1Up-RegulationConceptsIdiopathic pulmonary fibrosisPD-1Pulmonary fibrosisT cellsCollagen-1 productionPD-1 pathway blockadeCell death ligand 1T helper 17 (Th17) cellsPD-1 regulationIL-17A expressionProgressive inflammatory diseaseDeath ligand 1Helper 17 cellsT cell subsetsCell death 1Limited therapeutic optionsTGF-β1 productionLung disease pathophysiologyHuman lung fibroblastsPredominant CD4Bleomycin administrationIL-17ADeath-1Therapeutic optionsCell subsetsThe DNA repair transcriptome in severe COPD
Sauler M, Lamontagne M, Finnemore E, Herazo-Maya JD, Tedrow J, Zhang X, Morneau JE, Sciurba F, Timens W, Paré PD, Lee PJ, Kaminski N, Bossé Y, Gomez JL. The DNA repair transcriptome in severe COPD. European Respiratory Journal 2018, 52: 1701994. PMID: 30190272, PMCID: PMC6422831, DOI: 10.1183/13993003.01994-2017.Peer-Reviewed Original ResearchConceptsDNA damage toleranceDNA repairInadequate DNA repairSevere chronic obstructive pulmonary diseaseChronic obstructive pulmonary diseaseRepair pathwaysGene correlation network analysisIntegrative genomics approachNucleotide excision repair pathwayDNA repair pathwaysGene Set Enrichment AnalysisExcision repair pathwayGlobal transcriptomic profilesDNA repair genesDNA repair responseCorrelation network analysisCOPD severityGenomic approachesLung tissue transcriptomeTranscriptomic differencesTranscriptomic changesTranscriptomic patternsRNA sequencingTissue transcriptomesTranscriptomic profilesHypercapnia increases airway smooth muscle contractility via caspase-7–mediated miR-133a–RhoA signaling
Shigemura M, Lecuona E, Angulo M, Homma T, Rodríguez DA, Gonzalez-Gonzalez FJ, Welch LC, Amarelle L, Kim SJ, Kaminski N, Budinger GRS, Solway J, Sznajder JI. Hypercapnia increases airway smooth muscle contractility via caspase-7–mediated miR-133a–RhoA signaling. Science Translational Medicine 2018, 10 PMID: 30185650, PMCID: PMC6889079, DOI: 10.1126/scitranslmed.aat1662.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAgedAged, 80 and overAirway ResistanceAnimalsCalciumCalpainCarbon DioxideCaspase 7Chronic DiseaseDown-RegulationEnzyme ActivationFemaleHumansHypercapniaMaleMEF2 Transcription FactorsMice, Inbred C57BLMicroRNAsMiddle AgedMuscle ContractionMuscle, SmoothMyocytes, Smooth MusclePulmonary Disease, Chronic ObstructiveRhoA GTP-Binding ProteinSignal TransductionConceptsChronic obstructive pulmonary diseaseAirway smooth muscle cellsSmooth muscle cellsMouse airway smooth muscle cellsSevere chronic obstructive pulmonary diseaseHuman airway smooth muscle cellsAirway smooth muscle contractilityMuscle cellsCorrection of hypercapniaSmooth muscle cell contractionCohort of patientsObstructive pulmonary diseaseHigh airway resistanceSevere lung diseaseDevelopment of hypercapniaSmooth muscle contractilityMuscle cell contractionRas homolog family member AMyosin light chain phosphorylationAirway contractilityAirway contractionHypercapnic patientsCOPD severityPulmonary diseaseAirway resistance