2023
Acetate controls endothelial-to-mesenchymal transition
Zhu X, Wang Y, Soaita I, Lee H, Bae H, Boutagy N, Bostwick A, Zhang R, Bowman C, Xu Y, Trefely S, Chen Y, Qin L, Sessa W, Tellides G, Jang C, Snyder N, Yu L, Arany Z, Simons M. Acetate controls endothelial-to-mesenchymal transition. Cell Metabolism 2023, 35: 1163-1178.e10. PMID: 37327791, PMCID: PMC10529701, DOI: 10.1016/j.cmet.2023.05.010.Peer-Reviewed Original ResearchConceptsTGF-β signalingChronic vascular diseaseTGF-β receptor ALK5Mesenchymal transitionInduction of EndMTVascular diseaseMolecular basisPositive feedback loopReceptor ALK5Cellular levelSMADs 2Novel targetEndMT inductionMetabolic modulationMetabolic basisFibrotic stateSignalingPotential treatmentEndMTTGFDiseaseActivationInductionACSS2PDK4Correction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Lee C, He C, Park J, Lee J, Kamle S, Ma B, Akosman B, Cotez R, Chen E, Zhou Y, Herzog E, Ryu C, Peng X, Rosas I, Poli S, Bostwick C, Choi A, Elias J, Lee C. Correction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Science Alliance 2023, 6: e202302065. PMID: 37037591, PMCID: PMC10088146, DOI: 10.26508/lsa.202302065.Peer-Reviewed Original Research
2022
Endothelial Cell TGF-β (Transforming Growth Factor-Beta) Signaling Regulates Venous Adaptive Remodeling to Improve Arteriovenous Fistula Patency
Taniguchi R, Ohashi Y, Lee JS, Hu H, Gonzalez L, Zhang W, Langford J, Matsubara Y, Yatsula B, Tellides G, Fahmy TM, Hoshina K, Dardik A. Endothelial Cell TGF-β (Transforming Growth Factor-Beta) Signaling Regulates Venous Adaptive Remodeling to Improve Arteriovenous Fistula Patency. Arteriosclerosis Thrombosis And Vascular Biology 2022, 42: 868-883. PMID: 35510552, PMCID: PMC9233042, DOI: 10.1161/atvbaha.122.317676.Peer-Reviewed Original ResearchConceptsArteriovenous fistulaSMC proliferationAVF patencyCollagen densityMouse aortocaval fistula modelTGF-β receptor IArteriovenous fistula patencyAortocaval fistula modelInhibition of TGFPredetermined time pointsTGF-β inhibitionTGF-β signalingTGF-β receptorDisruption of TGFFistula patencyAVF failureWall thicknessVascular accessVenous remodelingSuccessful hemodialysisDoppler ultrasoundFistula modelReceptor IPatencyTGF
2020
The induction and function of the anti-inflammatory fate of TH17 cells
Xu H, Agalioti T, Zhao J, Steglich B, Wahib R, Vesely MCA, Bielecki P, Bailis W, Jackson R, Perez D, Izbicki J, Licona-Limón P, Kaartinen V, Geginat J, Esplugues E, Tolosa E, Huber S, Flavell RA, Gagliani N. The induction and function of the anti-inflammatory fate of TH17 cells. Nature Communications 2020, 11: 3334. PMID: 32620760, PMCID: PMC7335205, DOI: 10.1038/s41467-020-17097-5.Peer-Reviewed Original ResearchH19/TET1 axis promotes TGF‐β signaling linked to endothelial‐to‐mesenchymal transition
Cao T, Jiang Y, Li D, Sun X, Zhang Y, Qin L, Tellides G, Taylor HS, Huang Y. H19/TET1 axis promotes TGF‐β signaling linked to endothelial‐to‐mesenchymal transition. The FASEB Journal 2020, 34: 8625-8640. PMID: 32374060, PMCID: PMC7364839, DOI: 10.1096/fj.202000073rrrrr.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCoronary VesselsEpithelial-Mesenchymal TransitionHuman Umbilical Vein Endothelial CellsHumansMiceMice, Inbred C57BLMice, KnockoutMixed Function OxygenasesProto-Oncogene ProteinsRNA Processing, Post-TranscriptionalRNA, Long NoncodingSignal TransductionTransforming Growth Factor betaConceptsTGF-β signalingCardiovascular diseaseHuman umbilical vein endothelial cellsEndothelial cellsEndothelial activationMesenchymal transitionMouse pulmonary microvascular endothelial cellsPulmonary microvascular endothelial cellsHuman atherosclerotic coronary arteriesAtherosclerotic coronary arteriesMicrovascular endothelial cellsPrimary human umbilical vein endothelial cellsUmbilical vein endothelial cellsAortic endothelial cellsEndothelial dysfunctionVein endothelial cellsCoronary arteryRisk factorsHyperglycemic conditionsH19 expressionAberrant expressionEndMTH19 lncRNATET1 expressionMolecular underpinnings
2019
Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Cilfone N, Kauffman K, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson D, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz M, Pober J, Chittenden T, Tellides G, Simons M. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism 2019, 1: 912-926. PMID: 31572976, PMCID: PMC6767930, DOI: 10.1038/s42255-019-0102-3.Peer-Reviewed Original ResearchConceptsTGF-β signalingVascular inflammationDisease progressionPlaque growthProgressive vascular diseaseVessel wall inflammationChronic inflammatory responseSpecific therapeutic interventionsAtherosclerotic plaque growthHyperlipidemic micePlaque inflammationWall inflammationProinflammatory effectsVascular diseaseInflammatory responseVascular permeabilityAtherosclerotic plaquesAbnormal shear stressTherapeutic interventionsInflammationEndothelial TGFΒ signalingVessel wallAtherosclerosisLipid retention
2018
An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm
Lino Cardenas CL, Kessinger CW, Cheng Y, MacDonald C, MacGillivray T, Ghoshhajra B, Huleihel L, Nuri S, Yeri AS, Jaffer FA, Kaminski N, Ellinor P, Weintraub NL, Malhotra R, Isselbacher EM, Lindsay ME. An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm. Nature Communications 2018, 9: 1009. PMID: 29520069, PMCID: PMC5843596, DOI: 10.1038/s41467-018-03394-7.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAnimalsAortaAortic Aneurysm, ThoracicCell LineCell NucleusChromatinDisease Models, AnimalDNA HelicasesDNA MethylationFemaleFluorescent Antibody TechniqueHistone DeacetylasesHistonesHumansMaleMiceMice, KnockoutMuscle, Smooth, VascularMutationMyocytes, Smooth MuscleNuclear ProteinsPhenotypePrimary Cell CultureRepressor ProteinsRNA InterferenceRNA, Long NoncodingRNA, Small InterferingSignal TransductionTranscription FactorsTransforming Growth Factor betaConceptsChromatin-remodeling enzyme BRG1Contractile protein gene expressionProtein gene expressionLong noncoding RNA MALAT1Noncoding RNA MALAT1Bind chromatinTGF-β signalingTrimethylation modificationActomyosin cytoskeletonEpigenetic pathwaysContractile protein expressionGene expressionSimilar phenotypeRNA MALAT1Ternary complexBRG1HDAC9VSMC dysfunctionAortic aneurysmCytoskeletonProtein expressionPotential common mechanismsCommon mechanismSmooth muscle dysfunctionMutations
2015
Endothelial-to-mesenchymal transition drives atherosclerosis progression
Chen PY, Qin L, Baeyens N, Li G, Afolabi T, Budatha M, Tellides G, Schwartz MA, Simons M. Endothelial-to-mesenchymal transition drives atherosclerosis progression. Journal Of Clinical Investigation 2015, 125: 4514-4528. PMID: 26517696, PMCID: PMC4665771, DOI: 10.1172/jci82719.Peer-Reviewed Original ResearchConceptsProgression of atherosclerosisTGF-β signalingFGF receptor 1Left main coronary arteryMesenchymal transitionFGFR1 expressionDevelopment of EndMTMain coronary arteryTotal plaque burdenHigh-fat dietCultured human endothelial cellsDouble knockout miceEndothelial-specific deletionEarly time pointsCoronary atherosclerosisCoronary diseaseHuman endothelial cellsAtherosclerosis progressionPlaque burdenAtherosclerotic miceCoronary arteryInflammatory cytokinesAtherosclerotic lesionsNeointima formationClinical relevance
2014
Science Signaling Podcast: 23 September 2014
Simons M, VanHook A. Science Signaling Podcast: 23 September 2014. Science Signaling 2014, 7 DOI: 10.1126/scisignal.2005857.Peer-Reviewed Original ResearchTGF-β signalingMesenchymal transitionReceptor FGFR1Line blood vesselsFibroblast growth factor (FGF) pathwayEndothelial cellsTGF-β receptorCell biologyPolarized cellsGrowth factor pathwaysScience SignalingSignalingBlood vesselsFactor pathwayVascular homeostasisFGFNormal functionCellsFGFR1EndMTNormal conditionsMicroRNAsSenior authorBiologyHomeostasis
2013
Syndecan-2 Exerts Antifibrotic Effects by Promoting Caveolin-1–mediated Transforming Growth Factor-β Receptor I Internalization and Inhibiting Transforming Growth Factor-β1 Signaling
Shi Y, Gochuico BR, Yu G, Tang X, Osorio JC, Fernandez IE, Risquez CF, Patel AS, Shi Y, Wathelet MG, Goodwin AJ, Haspel JA, Ryter SW, Billings EM, Kaminski N, Morse D, Rosas IO. Syndecan-2 Exerts Antifibrotic Effects by Promoting Caveolin-1–mediated Transforming Growth Factor-β Receptor I Internalization and Inhibiting Transforming Growth Factor-β1 Signaling. American Journal Of Respiratory And Critical Care Medicine 2013, 188: 831-841. PMID: 23924348, PMCID: PMC3826270, DOI: 10.1164/rccm.201303-0434oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBleomycinBronchoalveolar LavageCaveolin 1Disease Models, AnimalGene Expression ProfilingGenetic MarkersHumansHydroxyprolineIdiopathic Pulmonary FibrosisIn Vitro TechniquesMacrophages, AlveolarMiceMice, TransgenicSignal TransductionSyndecan-2Tissue Array AnalysisTransforming Growth Factor beta1Up-RegulationConceptsHuman syndecan-2TGF-β1 target genesSyndecan-2Target genesIdiopathic pulmonary fibrosisEpithelial cell apoptosisAlveolar epithelial cellsEpithelial cellsTransforming Growth Factor-β1 SignalingCell apoptosisAntifibrotic effectsTGF-β1TGF-β signalingLung injuryPulmonary fibrosisAlveolar epithelial cell apoptosisExtracellular matrix productionTransgenic miceGrowth factor-β1 (TGF-β1) signalingMacrophage-specific overexpressionLung fibrosisMicroarray assayΒ1 signalingAlveolar macrophagesDownstream expressionA synthetic PPAR-γ agonist triterpenoid ameliorates experimental fibrosis: PPAR-γ-independent suppression of fibrotic responses
Wei J, Zhu H, Komura K, Lord G, Tomcik M, Wang W, Doniparthi S, Tamaki Z, Hinchcliff M, Distler JH, Varga J. A synthetic PPAR-γ agonist triterpenoid ameliorates experimental fibrosis: PPAR-γ-independent suppression of fibrotic responses. Annals Of The Rheumatic Diseases 2013, 73: 446-454. PMID: 23515440, PMCID: PMC4028127, DOI: 10.1136/annrheumdis-2012-202716.Peer-Reviewed Original ResearchMeSH KeywordsAdipogenesisAdultAnimalsBiopsyCells, CulturedCollagenDisease Models, AnimalDrug Evaluation, PreclinicalFemaleFibroblastsFibrosisHumansInfant, NewbornMiceMice, Inbred C57BLOleanolic AcidOrgan Culture TechniquesPPAR gammaProto-Oncogene Proteins c-aktScleroderma, SystemicSignal TransductionSkinTransforming Growth Factor betaConceptsSkin organ cultureHuman skin organ cultureAntifibrotic effectsDermal fibrosisExperimental fibrosisOrgan culturePeroxisome proliferator-activated receptor γModulation of fibrogenesisProliferator-activated receptor γHuman skin equivalentsPotential new therapiesPotential therapeutic strategyFibrotic gene expressionSynthetic oleanane triterpenoidComplementary mouse modelsControl of fibrosisPersistent fibroblast activationGrowth factor βTGF-β signalingEffects of CDDOSystemic sclerosisBleomycin injectionFibrogenic responseFibrotic activityMurine model
2012
FGF Regulates TGF-β Signaling and Endothelial-to-Mesenchymal Transition via Control of let-7 miRNA Expression
Chen PY, Qin L, Barnes C, Charisse K, Yi T, Zhang X, Ali R, Medina PP, Yu J, Slack FJ, Anderson DG, Kotelianski V, Wang F, Tellides G, Simons M. FGF Regulates TGF-β Signaling and Endothelial-to-Mesenchymal Transition via Control of let-7 miRNA Expression. Cell Reports 2012, 2: 1684-1696. PMID: 23200853, PMCID: PMC3534912, DOI: 10.1016/j.celrep.2012.10.021.Peer-Reviewed Original ResearchConceptsFibroblast growth factorEndo-MTMesenchymal transitionGrowth factorNormal endothelial functionBlood vessel functionTGF-β signalingEndothelial functionVascular pathologyEndothelial homeostasisNeointima formationVessel functionΒ ligandMiRNA levelsMiRNA expressionActivationExpressionUnexpected roleLess Is More: Unveiling the Functional Core of Hematopoietic Stem Cells through Knockout Mice
Rossi L, Lin K, Boles N, Yang L, King K, Jeong M, Mayle A, Goodell M. Less Is More: Unveiling the Functional Core of Hematopoietic Stem Cells through Knockout Mice. Cell Stem Cell 2012, 11: 302-317. PMID: 22958929, PMCID: PMC3461270, DOI: 10.1016/j.stem.2012.08.006.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHematopoietic stem cellsHSC functionSomatic stem cell typesCell cycle controlStem cellsPTEN/AKTKey regulatory pathwaysStem cell typesTGF-β signalingKnockout miceHSC biologyRegulatory pathwaysCycle controlGenetic analysisCell typesFunctional coreFunctional modulesCellsWntCohesive pictureGenesSignalingBiologyAktMicemicroRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma
Genovese G, Ergun A, Shukla SA, Campos B, Hanna J, Ghosh P, Quayle SN, Rai K, Colla S, Ying H, Wu CJ, Sarkar S, Xiao Y, Zhang J, Zhang H, Kwong L, Dunn K, Wiedemeyer WR, Brennan C, Zheng H, Rimm DL, Collins JJ, Chin L. microRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma. Cancer Discovery 2012, 2: 736-749. PMID: 22750848, PMCID: PMC3911772, DOI: 10.1158/2159-8290.cd-12-0111.Peer-Reviewed Original ResearchConceptsMultidimensional cancer genomic dataPromoter enrichment analysisCancer genomic dataNovel regulatorGenomic dataContext likelihoodEnrichment analysisPutative regulatory networksFunctional genetic screensDifferent genetic elementsGenetic screenTGF-β signalingTranscriptional networksPlatelet-derived growth factorMRNA nodesGenome spaceRegulatory networksTranscriptomic networksBiology of cancerNovel regulationGenetic elementsTumor suppressorSilico analysisDirect regulationNew pathogenetic insightsZyxin Is a Transforming Growth Factor-β (TGF-β)/Smad3 Target Gene That Regulates Lung Cancer Cell Motility via Integrin α5β1*
Mise N, Savai R, Yu H, Schwarz J, Kaminski N, Eickelberg O. Zyxin Is a Transforming Growth Factor-β (TGF-β)/Smad3 Target Gene That Regulates Lung Cancer Cell Motility via Integrin α5β1*. Journal Of Biological Chemistry 2012, 287: 31393-31405. PMID: 22778267, PMCID: PMC3438968, DOI: 10.1074/jbc.m112.357624.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Adhesion MoleculesCell Line, TumorCell MovementFocal AdhesionsGene SilencingHumansIntegrin alpha5beta1Intercellular JunctionsLung NeoplasmsMiceMice, Mutant StrainsMicrofilament ProteinsPhosphoproteinsProto-Oncogene Proteins p21(ras)Signal TransductionSmad3 ProteinTransforming Growth Factor beta1ZyxinConceptsEpithelial-mesenchymal transitionCancer cell motilityCell motilityFocal adhesionsZyxin expressionCell-extracellular matrix adhesionLung cancer cellsFocal adhesion proteinsSingle cell motilityCell-cell junctionsCell adherens junctionsNovel functional targetSingle cell migrationLung cancer cell motilityCancer cellsNovel direct targetZyxin geneTGF-β signalingTumor suppressor effectActin cytoskeletonAdherens junctionsCytoskeletal organizationZyxinTarget genesAdhesion proteinsLead induces an osteoarthritis‐like phenotype in articular chondrocytes through disruption of TGF‐β signaling
Holz JD, Beier E, Sheu T, Ubayawardena R, Wang M, Sampson ER, Rosier RN, Zuscik M, Puzas JE. Lead induces an osteoarthritis‐like phenotype in articular chondrocytes through disruption of TGF‐β signaling. Journal Of Orthopaedic Research® 2012, 30: 1760-1766. PMID: 22517267, PMCID: PMC3839422, DOI: 10.1002/jor.22117.Peer-Reviewed Original ResearchConceptsLead treatmentOsteoarthritis-like phenotypeNormal chondrocyte phenotypeDose-dependent mannerArticular chondrocytesTGF-β signalingActive caspase-3MMP13 activityLead exposureHigher level leadType II collagenVivo exposureCollagen levelsNovel targetType X collagenCaspase-3Articular surfaceEnvironmental toxinsLead toxicityII collagenReporter activityTreatmentArticular cartilageDosePhenotypic shift
2011
LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L
Lucas CL, Workman CJ, Beyaz S, LoCascio S, Zhao G, Vignali DA, Sykes M. LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L. Blood 2011, 117: 5532-5540. PMID: 21422469, PMCID: PMC3109721, DOI: 10.1182/blood-2010-11-318675.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigens, CDAntigens, SurfaceApoptosis Regulatory ProteinsB7-1 AntigenB7-H1 AntigenBone Marrow TransplantationCD4-Positive T-LymphocytesCD40 LigandCD8-Positive T-LymphocytesCTLA-4 AntigenFemaleImmune ToleranceLymphocyte Activation Gene 3 ProteinMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalPeptidesProgrammed Cell Death 1 Ligand 2 ProteinProgrammed Cell Death 1 ReceptorSignal TransductionTransforming Growth Factor betaTransplantation, HomologousConceptsT cell toleranceCD4 T cell tolerancePeripheral CD8PD-1LAG-3T cellsCD8 T cell tolerance inductionPD-1/PD-L1 pathwayCD8 T cell tolerancePD-1 inhibitory pathwayT cell tolerance inductionAdoptive transfer studiesAllogeneic BM transplantationPD-L1 pathwayAlloreactive T cellsMixed hematopoietic chimerismT cell-intrinsic requirementB7.1/B7.2Cell-intrinsic requirementTGF-β signalingAllogeneic BMTPD-L1Mixed chimerasPD-L2Tolerance induction
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