2021
Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Chandran RR, Xie Y, Gallardo-Vara E, Adams T, Garcia-Milian R, Kabir I, Sheikh AQ, Kaminski N, Martin KA, Herzog EL, Greif DM. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nature Communications 2021, 12: 7179. PMID: 34893592, PMCID: PMC8664937, DOI: 10.1038/s41467-021-27499-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDisease Models, AnimalDown-RegulationExtracellular MatrixFemaleFibroblastsFibrosisHumansKruppel-Like Factor 4LungLung InjuryMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsReceptor, Platelet-Derived Growth Factor betaRespiratory Tract DiseasesSignal TransductionTransforming Growth Factor betaConceptsMesenchymal cell typesPlatelet-derived growth factor receptorSmooth muscle actinLung fibrosisKruppel-like factor 4Forkhead box M1Growth factor receptorCell transitionCell typesExtracellular matrixDistinct rolesKLF4Box M1C chemokine ligandMesenchymal cell subtypesFactor receptorPro-fibrotic effectsFactor 4PDGFRMesenchymeCellsMacrophage accumulationKLF4 levelsChemokine ligandLung fibrogenesis
2018
Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells
Misra A, Feng Z, Chandran RR, Kabir I, Rotllan N, Aryal B, Sheikh AQ, Ding L, Qin L, Fernández-Hernando C, Tellides G, Greif DM. Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nature Communications 2018, 9: 2073. PMID: 29802249, PMCID: PMC5970166, DOI: 10.1038/s41467-018-04447-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisBone Marrow TransplantationCell MovementCell ProliferationCell TransdifferentiationCells, CulturedCholesterolDisease Models, AnimalFemaleHumansIntegrin beta3MacrophagesMaleMiceMice, Inbred C57BLMice, Knockout, ApoEMuscle, Smooth, VascularMyocytes, Smooth MusclePlaque, AtheroscleroticConceptsSmooth muscle cellsPre-existing smooth muscle cellsAtherosclerotic plaquesPlaque cellsToll-like receptor 4 expressionSmooth muscle-derived cellsBone marrow-derived cellsSingle smooth muscle cellsAtherosclerotic plaque cellsReceptor 4 expressionMarrow-derived cellsBone marrow resultsMuscle-derived cellsIntegrin β3 levelsMacrophage-like phenotypeCD36 levelsMarrow resultsSMC proliferationPlaque coresSMC progenitorsMuscle cellsIntegrin β3AtherogenesisPlaquesIntegrin beta3Pericyte ALK5/TIMP3 Axis Contributes to Endothelial Morphogenesis in the Developing Brain
Dave JM, Mirabella T, Weatherbee SD, Greif DM. Pericyte ALK5/TIMP3 Axis Contributes to Endothelial Morphogenesis in the Developing Brain. Developmental Cell 2018, 44: 665-678.e6. PMID: 29456135, PMCID: PMC5871595, DOI: 10.1016/j.devcel.2018.01.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood-Brain BarrierBrainEmbryo, MammalianEndothelium, VascularFemaleHumansIntracranial HemorrhagesMaleMiceMice, Inbred C57BLMice, KnockoutMorphogenesisPericytesProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IReceptors, Transforming Growth Factor betaSignal TransductionTissue Inhibitor of Metalloproteinase-3ConceptsEndothelial morphogenesisReceptor-like kinasesBlood-brain barrierActivin receptor-like kinaseGerminal matrixGerminal matrix hemorrhage-intraventricular hemorrhageMurine embryosEC morphogenesisEndothelial cellsEC hyperproliferationMorphogenesisMatrix metalloproteinase-3Glial precursorsBasement membrane collagenMatrix metalloproteinase activityBBB developmentMutantsVascular stabilityALK5Brain pericytesAbnormal dilationSubstantial therapeutic potentialMetalloproteinase-3Membrane collagenTissue inhibitor
2017
mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice
Jiao Y, Li G, Li Q, Ali R, Qin L, Li W, Qyang Y, Greif DM, Geirsson A, Humphrey JD, Tellides G. mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice. Arteriosclerosis Thrombosis And Vascular Biology 2017, 37: 1657-1666. PMID: 28751568, PMCID: PMC5574180, DOI: 10.1161/atvbaha.117.309653.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesCell ProliferationCollagenElastinEverolimusFocal Adhesion Kinase 1Genetic Predisposition to DiseaseHumansImatinib MesylateMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Mechanotransduction, CellularMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesMuscle, Smooth, VascularPhenotypePhosphorylationProtein Kinase InhibitorsSirolimusTime FactorsTOR Serine-Threonine KinasesVascular StiffnessWilliams SyndromeConceptsElastin deficiencyCollagen accumulationArterial phenotypeNull miceGrowth factorSmooth muscle cell proliferationMuscle cell proliferationEarly postnatal deathInhibition of mTORAortic fibrosisAortic obstructionMedial thickeningAortic stiffeningNeonatal deathLuminal stenosisPharmacological blockadeAbsence of elastinThoracic aortaTherapeutic benefitJuvenile micePostnatal deathMTOR inhibitionAortaHeterozygous lossMice
2016
Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis
Misra A, Sheikh AQ, Kumar A, Luo J, Zhang J, Hinton RB, Smoot L, Kaplan P, Urban Z, Qyang Y, Tellides G, Greif DM. Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis. Journal Of Experimental Medicine 2016, 213: 451-463. PMID: 26858344, PMCID: PMC4813675, DOI: 10.1084/jem.20150688.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsMutant miceTherapeutic strategiesAortic stenosis patientsAortic smooth muscle cellsSupravalvular aortic stenosisAttractive therapeutic strategyIntegrin β3 levelsAortic pathologyAortic stenosisStenosis patientsArterial diseaseLumen lossPathological featuresArterial mediaLarge arteriesAortic mediaElastin deficiencyPharmacological inhibitionMuscle cellsStenosisMicePathological stenosisExplant culturesSVAS patients
2015
Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension
Sheikh AQ, Misra A, Rosas IO, Adams RH, Greif DM. Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension. Science Translational Medicine 2015, 7: 308ra159. PMID: 26446956, PMCID: PMC4629985, DOI: 10.1126/scitranslmed.aaa9712.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsKruppel-like factor 4Pulmonary hypertensionSmooth muscleHypoxia-induced pulmonary hypertensionPathogenesis of PHPulmonary artery blood pressureSMC progenitorsArteriole smooth muscleArtery blood pressureSmooth muscle cell progenitorsCardiovascular disease pathogenesisPlatelet-derived growth factor receptorHypoxia-induced expressionGrowth factor receptorPH patientsBlood pressurePulmonary arteriolesVascular disordersTherapeutic strategiesDisease pathogenesisKLF4 levelsKLF4 expressionDistal extensionMuscle cells
2012
An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension
Kim J, Kang Y, Kojima Y, Lighthouse JK, Hu X, Aldred MA, McLean DL, Park H, Comhair SA, Greif DM, Erzurum SC, Chun HJ. An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension. Nature Medicine 2012, 19: 74-82. PMID: 23263626, PMCID: PMC3540168, DOI: 10.1038/nm.3040.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApelinCell MovementCell ProliferationCells, CulturedCulture Media, ConditionedDown-RegulationEndothelial CellsFamilial Primary Pulmonary HypertensionFibroblast Growth Factor 2HumansHypertension, PulmonaryIntercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLMice, KnockoutMicroRNAsMuscle, Smooth, VascularMyocytes, Smooth MusclePulmonary ArteryRatsReceptor, Fibroblast Growth Factor, Type 1RNA InterferenceRNA, Small InterferingSignal TransductionVascular DiseasesConceptsPulmonary arterial hypertensionArterial hypertensionVascular smooth muscle cellsPulmonary endothelial cellsSmooth muscle cellsEndothelial cell proliferationPulmonary hypertensionPeptide apelinCytokine productionRat modelVascular homeostasisHypertensionMiR-503MiR-424Endothelial cellsCell proliferation
2010
Targeting Robo4-Dependent Slit Signaling to Survive the Cytokine Storm in Sepsis and Influenza
London NR, Zhu W, Bozza FA, Smith MC, Greif DM, Sorensen LK, Chen L, Kaminoh Y, Chan AC, Passi SF, Day CW, Barnard DL, Zimmerman GA, Krasnow MA, Li DY. Targeting Robo4-Dependent Slit Signaling to Survive the Cytokine Storm in Sepsis and Influenza. Science Translational Medicine 2010, 2: 23ra19. PMID: 20375003, PMCID: PMC2875996, DOI: 10.1126/scitranslmed.3000678.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCadherinsCapillary PermeabilityCateninsCell LineCytokinesDelta CateninDisease Models, AnimalEndothelium, VascularHumansInfluenza A Virus, H5N1 SubtypeIntercellular Signaling Peptides and ProteinsLipopolysaccharidesMiceMice, Inbred C57BLNerve Tissue ProteinsOrthomyxoviridae InfectionsProtein BindingProtein StabilityProtein TransportReceptors, Cell SurfaceReceptors, ImmunologicSepsisSignal TransductionConceptsInnate immune responseImmune systemCytokine stormImmune responseInfectious agentsHost innate immune responseCurrent medical therapyMultiple inflammatory cytokinesBacterial endotoxin exposureHost immune systemInnate immune systemMultiple infectious agentsAdditional immune responsesPolymicrobial sepsisMedical therapyOrgan failureInflammatory cytokinesCytokine releaseTumor necrosisEndotoxin exposureTissue edemaInterleukin-1betaVascular permeabilityTherapeutic strategiesAnimal models