2018
T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K
Rao GK, Wong A, Collinge M, Sarhan J, Yarovinsky TO, Ramgolam VS, Gaestel M, Pardi R, Bender JR. T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K. PLOS ONE 2018, 13: e0201103. PMID: 30048492, PMCID: PMC6065199, DOI: 10.1371/journal.pone.0201103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Culture TechniquesCytoplasmELAV-Like Protein 1Heterogeneous-Nuclear RibonucleoproteinsHumansIntracellular Signaling Peptides and ProteinsJurkat CellsLymphocyte Function-Associated Antigen-1Mice, Inbred C57BLMice, KnockoutProtein Serine-Threonine KinasesProteomeRNA StabilityRNA, MessengerSignal TransductionT-LymphocytesConceptsKinase MK2Β2-integrin lymphocyte function-associated antigen-1AU-rich elementsLymphocyte function-associated antigen-1Integrin lymphocyte function-associated antigen-1HuR localizationProtein HuR.Key regulatorMRNA stabilizationCritical activatorCytoplasmic translocationHuR activitySequential activationHuRIntricate processFunction-associated antigen-1MRNAEngagement resultsMK2Antigen 1H1ActivationHnRNPsHuR.Transcripts
2016
Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production
Ceneri N, Zhao L, Young BD, Healy A, Coskun S, Vasavada H, Yarovinsky TO, Ike K, Pardi R, Qin L, Qin L, Tellides G, Hirschi K, Meadows J, Soufer R, Chun HJ, Sadeghi M, Bender JR, Morrison AR. Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production. Arteriosclerosis Thrombosis And Vascular Biology 2016, 37: 328-340. PMID: 27834690, PMCID: PMC5269510, DOI: 10.1161/atvbaha.116.308507.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedCoronary Artery DiseaseCoronary VesselsFemaleGenetic Predisposition to DiseaseHumansInflammation MediatorsInterleukin 1 Receptor Antagonist ProteinInterleukin-1betaMacrophagesMaleMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropeptidesPhenotypePlaque, AtheroscleroticPrognosisRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSignal TransductionTransfectionUp-RegulationVascular CalcificationConceptsCoronary calcium burdenIL-1β expressionCalcium burdenSerum IL-1β levelsElevated IL-1βIL-1β levelsCoronary artery diseaseInterleukin-1β expressionCalcified coronary arteryCardiovascular deathCardiovascular eventsArtery diseaseIndependent predictorsClinical outcomesVascular calcificationCoronary arteryIL-1βPlaque calciumAtherosclerotic calcificationExperimental atherogenesisInflammatory regulatorsMacrophage interleukinAtherosclerotic plaquesTherapeutic targetProgressive calcificationThe molecular actions of oestrogen in the regulation of vascular health
Usselman CW, Stachenfeld NS, Bender JR. The molecular actions of oestrogen in the regulation of vascular health. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2016, 101: 356-361. PMID: 26778523, PMCID: PMC4947570, DOI: 10.1113/ep085148.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAction of estrogenVascular healthFunctional outcomeHormone therapy trialsNormal endothelial functionVascular smooth muscleMembrane-bound estrogen receptorMolecular actionsPremenopausal womenEndothelial functionEstrogen actionCardiovascular diseaseEstrogen receptorSmooth muscleBeneficial actionsTherapy trialsEstrogenExperimental animalsVascular structuresFindings of studiesVasculatureWomenHealthMolecular mechanismsOutcomes
2014
Chemokine-coupled β2 integrin–induced macrophage Rac2–Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis
Morrison AR, Yarovinsky TO, Young BD, Moraes F, Ross TD, Ceneri N, Zhang J, Zhuang ZW, Sinusas AJ, Pardi R, Schwartz MA, Simons M, Bender JR. Chemokine-coupled β2 integrin–induced macrophage Rac2–Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis. Journal Of Experimental Medicine 2014, 211: 1957-1968. PMID: 25180062, PMCID: PMC4172219, DOI: 10.1084/jem.20132130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriesCD18 AntigensDNA PrimersFlow CytometryHumansMiceMice, Inbred C57BLMonocytesNeovascularization, PhysiologicNonmuscle Myosin Type IIARac GTP-Binding ProteinsReal-Time Polymerase Chain ReactionReceptors, CCR2RNA StabilityVascular Endothelial Growth Factor AX-Ray MicrotomographyConceptsMyosin IIASignal transduction eventsHuR translocationRapid nuclearTransduction eventsProteomic analysisProtein HuR.Induction of arteriogenesisMRNA stabilityMRNA stabilizationNovel roleCytosolic translocationMyosin-9ICAM-1 adhesionReceptor engagementDevelopmental vasculogenesisCellular effectorsMolecular triggersTranslocationHeavy chainGrowth factorMyeloid cellsVascular endothelial growth factorKey molecular triggerCCL2 stimulationCeramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis
Mehra VC, Jackson E, Zhang XM, Jiang XC, Dobrucki LW, Yu J, Bernatchez P, Sinusas AJ, Shulman GI, Sessa WC, Yarovinsky TO, Bender JR. Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis. American Journal Of Pathology 2014, 184: 1562-1576. PMID: 24606881, PMCID: PMC4005977, DOI: 10.1016/j.ajpath.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaArteriesCattleCeramidesDiet, High-FatEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesHaploinsufficiencyHindlimbHumansIschemiaMice, Inbred C57BLNeovascularization, PhysiologicNitric OxideNitric Oxide Synthase Type IIIPalmitic AcidPhosphorylationProtein Phosphatase 2Proto-Oncogene Proteins c-aktSerine C-PalmitoyltransferaseSignal TransductionVascular Endothelial Growth Factor AConceptsPP2A inhibitor okadaic acidProtein phosphatase 2AInhibitor okadaic acidVEGF-induced signalingSerine palmitoyltransferase inhibitor myriocinDe novo ceramide synthesisPhosphatase 2AENOS agonistsNovo ceramide synthesisPalmitic acidAngiogenic responsePotential molecular targetsOkadaic acidEndothelial cellsEarly speciesEndothelial cell responsesCord formationVEGFR2 phosphorylationSaturated free fatty acidVEGF resistanceCeramide synthesisResistance mechanismsMolecular targetsVascular homeostasisPhosphorylationEndothelial estrogen receptor isoforms and cardiovascular disease
Kim KH, Young BD, Bender JR. Endothelial estrogen receptor isoforms and cardiovascular disease. Molecular And Cellular Endocrinology 2014, 389: 65-70. PMID: 24530925, PMCID: PMC4040324, DOI: 10.1016/j.mce.2014.02.001.BooksConceptsNitric oxideFull-length ERαPlasma membrane-associated estrogen receptorOvarian steroid hormonesMembrane-associated estrogen receptorsEstrogen receptor isoformsCardiovascular diseaseEstrogen receptorEndothelial responseRapid E2ER isoformsSteroid hormonesReceptor isoformsVascular cellsClinical contextFavorable effectTissue responseEndothelial signalingVascular systemERαER46Transcriptional modulationTransmembrane moleculesSignalingRapid endothelial responsesThe PAR complex controls the spatiotemporal dynamics of F-actin and the MTOC in directionally migrating leukocytes
Crespo CL, Vernieri C, Keller PJ, Garrè M, Bender JR, Wittbrodt J, Pardi R. The PAR complex controls the spatiotemporal dynamics of F-actin and the MTOC in directionally migrating leukocytes. Journal Of Cell Science 2014, 127: 4381-4395. PMID: 25179599, PMCID: PMC4197085, DOI: 10.1242/jcs.146217.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAdaptor Proteins, Signal TransducingAnimalsAnimals, Genetically ModifiedCarrier ProteinsCell MovementCell PolarityCells, CulturedLeukocytesMicrotubule-Organizing CenterMultiprotein ComplexesMutationOryziasProtein Kinase CProtein TransportRho-Associated KinasesZebrafishZebrafish ProteinsConceptsAtypical protein kinase CMicrotubule organizing centerPAR-6Par complexPAR-3Protein kinase CRegulated interactionFish larvaeMyeloid cellsGenetic manipulationPolarizing cuesKinase activationCytoskeletal changesF-actinKinase COrganizing centerFunctional polarizationRho kinase activationThree-dimensional environmentTraction forceCellsSpatiotemporal dynamicsLeukocyte migrationMigrationComplexes
2013
Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis
Nie L, Guo X, Esmailzadeh L, Zhang J, Asadi A, Collinge M, Li X, Kim JD, Woolls M, Jin SW, Dubrac A, Eichmann A, Simons M, Bender JR, Sadeghi MM. Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis. Journal Of Clinical Investigation 2013, 123: 5082-5097. PMID: 24177422, PMCID: PMC3859420, DOI: 10.1172/jci67752.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBlood VesselsCadherinsCells, CulturedEar, ExternalEndothelium, VascularHindlimbHuman Umbilical Vein Endothelial CellsHumansIschemiaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNeuropilinsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 2Retinal VesselsRNA InterferenceRNA, Small InterferingVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ZebrafishZebrafish ProteinsConceptsSmooth muscle cell-derived neuropilin-like proteinAberrant blood vessel formationNormal vascular developmentProtein tyrosineTC-PTPTransmembrane proteinTherapeutic targetBlood vessel formationVEGF responseNegative regulatorDevelopmental angiogenesisVEGFR-2Vascular developmentAttractive therapeutic targetESDNAngiogenesis regulationVE-cadherinVessel formationEC proliferationComplex formationRegulatorProteinNeuropilin expressionVEGF receptorsEndothelial VEGF
2012
Molecular Imaging of Vascular Endothelial Growth Factor Receptors in Graft Arteriosclerosis
Zhang J, Razavian M, Tavakoli S, Nie L, Tellides G, Backer JM, Backer MV, Bender JR, Sadeghi MM. Molecular Imaging of Vascular Endothelial Growth Factor Receptors in Graft Arteriosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2012, 32: 1849-1855. PMID: 22723442, PMCID: PMC3401339, DOI: 10.1161/atvbaha.112.252510.Peer-Reviewed Original ResearchConceptsGraft arteriosclerosisArtery graftVascular remodelingAllogeneic human peripheral blood mononuclear cellsHuman coronary artery segmentsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsSevere combined immunodeficiency miceVEGF receptorsVascular endothelial growth factor receptorLate organ failureHuman coronary artery graftsSolid organ transplantationCoronary artery graftsEndothelial growth factor receptorBlood mononuclear cellsCoronary artery segmentsCombined immunodeficiency miceReceptor 2 expressionVEGF receptor-2 expressionMolecular imagingSignificant neointima formationVascular endothelial growth factor signalingVEGF receptor 1Growth factor receptorMacrophage β2 Integrin–Mediated, HuR-Dependent Stabilization of Angiogenic Factor–Encoding mRNAs in Inflammatory Angiogenesis
Zhang J, Modi Y, Yarovinsky T, Yu J, Collinge M, Kyriakides T, Zhu Y, Sessa WC, Pardi R, Bender JR. Macrophage β2 Integrin–Mediated, HuR-Dependent Stabilization of Angiogenic Factor–Encoding mRNAs in Inflammatory Angiogenesis. American Journal Of Pathology 2012, 180: 1751-1760. PMID: 22322302, PMCID: PMC3349897, DOI: 10.1016/j.ajpath.2011.12.025.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAnimalsCD18 AntigensCell AdhesionCells, CulturedDisease Models, AnimalELAV ProteinsGene Expression RegulationGene Knockout TechniquesHindlimbInflammationIschemiaMacrophagesMiceMice, KnockoutMuscle, SkeletalNeovascularization, PathologicReal-Time Polymerase Chain ReactionRNA, MessengerConceptsKnockout miceAngiogenic factorsT cell cytokine productionIntercellular adhesion molecule-1Blood flow recoveryFemoral artery ligationLittermate wild-type controlsVascular endothelial growth factorBone marrow-derived macrophagesMatrix metalloproteinase-9Adhesion molecule-1Endothelial growth factorMarrow-derived macrophagesSoluble factor productionWild-type controlsArtery ligationLigand intercellular adhesion molecule-1Cytokine productionInflammatory angiogenesisMetalloproteinase-9Tissue ischemiaInflammatory stimuliMolecule-1Macrophage productionNeovascular response
2010
T Cell LFA-1 Engagement Induces HuR-Dependent Cytokine mRNA Stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 Signaling Cascade
Ramgolam VS, DeGregorio SD, Rao GK, Collinge M, Subaran SS, Markovic-Plese S, Pardi R, Bender JR. T Cell LFA-1 Engagement Induces HuR-Dependent Cytokine mRNA Stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 Signaling Cascade. PLOS ONE 2010, 5: e14450. PMID: 21206905, PMCID: PMC3012057, DOI: 10.1371/journal.pone.0014450.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceCytokinesELAV ProteinsELAV-Like Protein 1GTP PhosphohydrolasesHumansIntegrinsInterferon-gammaLymphocyte Function-Associated Antigen-1MAP Kinase Kinase 3MiceMice, Inbred C57BLNeuropeptidesP38 Mitogen-Activated Protein KinasesProto-Oncogene Proteins c-vavRac GTP-Binding ProteinsRac1 GTP-Binding ProteinRNA-Binding ProteinsSignal TransductionT-LymphocytesTumor Necrosis Factor-alpha
2009
Membrane-initiated actions of estrogen on the endothelium
Kim KH, Bender JR. Membrane-initiated actions of estrogen on the endothelium. Molecular And Cellular Endocrinology 2009, 308: 3-8. PMID: 19549586, PMCID: PMC2701909, DOI: 10.1016/j.mce.2009.03.025.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNumerous signal transduction cascadesSignal transduction cascadeNitric oxideEndothelial cellsNon-genomic actionsAction of estrogenNitric oxide synthaseCaveolar membranesEstrogen receptor alphaTransduction cascadeC-SrcN-terminusShort isoformHuman endothelial cellsRapid activationProduct nitric oxideVascular studiesOxide synthaseReceptor alphaEstrogenVascular structuresER46Favorable effectCritical role
2008
Rac, PAK, and eNOS ACTion
Rao GK, Bender JR. Rac, PAK, and eNOS ACTion. Circulation Research 2008, 103: 328-330. PMID: 18703782, DOI: 10.1161/circresaha.108.182238.Peer-Reviewed Original ResearchTargeted inactivation of the COP9 signalosome impairs multiple stagesof T cell development
Panattoni M, Sanvito F, Basso V, Doglioni C, Casorati G, Montini E, Bender JR, Mondino A, Pardi R. Targeted inactivation of the COP9 signalosome impairs multiple stagesof T cell development. Journal Of Experimental Medicine 2008, 205: 465-477. PMID: 18268034, PMCID: PMC2271025, DOI: 10.1084/jem.20070725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-X ProteinCell CycleCell LineCell ProliferationCOP9 Signalosome ComplexCyclin-Dependent Kinase Inhibitor p16DNA RepairFemaleHomeodomain ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesNF-kappa BPeptide HydrolasesProto-Oncogene Proteins c-bcl-2Receptors, Antigen, T-CellRNA, MessengerT-LymphocytesTumor Suppressor Protein p53Ubiquitin-Protein LigasesConceptsCOP9 signalosomeCSN5/Jab1Genetic programBcl-2 family membersGenetic complementation analysisBcl-xL/BclS-phase progressionDistinct developmental stagesCell cycle progressionT cell developmentComplementation analysisLower organismsCatalytic subunitPositive selectionTranscription factorsDNA repairCycle progressionCell developmentThymocyte survivalDevelopmental stagesNF-kappaB pathwayTransgenic backgroundPhase progressionRapid turnoverEffector moleculesVascular cell signaling by membrane estrogen receptors
Kim KH, Moriarty K, Bender JR. Vascular cell signaling by membrane estrogen receptors. Steroids 2008, 73: 864-869. PMID: 18325557, PMCID: PMC2519041, DOI: 10.1016/j.steroids.2008.01.008.Peer-Reviewed Original ResearchConceptsNumerous signal transduction cascadesEndothelial nitric oxide synthaseCaveolin-1 interactionSignal transduction cascadeEndothelial cellsNon-genomic actionsTranscriptional regulationPI3K/AktMembrane estrogen receptorsCaveolar membranesTransduction cascadeCell signalingC-SrcN-terminusHuman endothelial cellsRapid activationMolecular studiesConsequent activationVascular cellsNumerous animalsNitric oxideMultiple biological effectsEstrogen receptor alphaFavorable estrogenic effectsER46
2007
Variant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation
Li L, Hisamoto K, Kim KH, Haynes MP, Bauer PM, Sanjay A, Collinge M, Baron R, Sessa WC, Bender JR. Variant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 16468-16473. PMID: 17921256, PMCID: PMC2034248, DOI: 10.1073/pnas.0704315104.Peer-Reviewed Original ResearchConceptsC-SrcC-Src kinase activityTyrosine kinase c-SrcRapid signal transductionKinase c-SrcC-Src functionC-Src kinaseEndothelial NO synthase activationENOS activationMembrane recruitmentSignal transductionComplex assemblyPlasma membraneKinase activityOestrogen receptor-alpha variantsVenous endothelial cellsER46Pathway activationHormonal stimuliCritical roleArterial responseNO synthase activationSynthase activationStructural requirementsEndothelial cellsESDN Is a Marker of Vascular Remodeling and Regulator of Cell Proliferation in Graft Arteriosclerosis
Sadeghi MM, Esmailzadeh L, Zhang J, Guo X, Asadi A, Krassilnikova S, Fassaei HR, Luo G, Al‐Lamki R, Takahashi T, Tellides G, Bender JR, Rodriguez ER. ESDN Is a Marker of Vascular Remodeling and Regulator of Cell Proliferation in Graft Arteriosclerosis. American Journal Of Transplantation 2007, 7: 2098-2105. PMID: 17697260, DOI: 10.1111/j.1600-6143.2007.01919.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCell ProliferationCells, CulturedCoronary Artery DiseaseCoronary VesselsDisease Models, AnimalHumansImmunohistochemistryMembrane ProteinsMiceMice, SCIDMuscle, Smooth, VascularReverse Transcriptase Polymerase Chain ReactionRNATissue TransplantationTransplantation, HomologousUp-RegulationConceptsGraft arteriosclerosisVascular remodelingCell proliferationSevere combined immunodeficient (SCID) miceInjury-induced vascular remodelingCombined Immunodeficient MiceHuman coronary arteriesVascular smooth muscle cell culturesVascular cell proliferationSmooth muscle cell culturesCell reconstitutionCoronary arteryImmunodeficient miceVSMC proliferationNormal arteriesArteryHuman coronaryMuscle cell culturesDiagnostic targetsHuman arteriesHigh levelsRemodelingSmooth muscle cell-derived neuropilin-like proteinArteriosclerosisProliferationActivated αvβ3 Integrin Targeting in Injury-Induced Vascular Remodeling
Sadeghi MM, Bender JR. Activated αvβ3 Integrin Targeting in Injury-Induced Vascular Remodeling. Trends In Cardiovascular Medicine 2007, 17: 5-10. PMID: 17210471, DOI: 10.1016/j.tcm.2006.07.003.Peer-Reviewed Original Research
2006
Estrogen Receptor-Mediated Rapid Signaling
Moriarty K, Kim KH, Bender JR. Estrogen Receptor-Mediated Rapid Signaling. Endocrinology 2006, 147: 5557-5563. PMID: 16946015, DOI: 10.1210/en.2006-0729.Peer-Reviewed Original ResearchConceptsMembrane estrogen receptorsPlasma membrane-associated formSplice variantsMembrane-associated formTranscriptional activationMultimolecular complexesRapid signalingSignaling cascadesMolecular componentsSpecific tissuesER splice variantsMolecular levelSpecific fashionEnzymatic pathwaysEstrogen receptorEstrogen responseNuclear responsePathwayPhysiological outcomesReceptorsComplexesSignalingVariantsVascular endotheliumRapid responsePathophysiology of leukocyte–tissue interactions
Molteni R, Fabbri M, Bender JR, Pardi R. Pathophysiology of leukocyte–tissue interactions. Current Opinion In Cell Biology 2006, 18: 491-498. PMID: 16904306, DOI: 10.1016/j.ceb.2006.08.001.Peer-Reviewed Original Research