2024
SUMOylation Fine-Tunes Endothelial HEY1 in the Regulation of Angiogenesis
Ren R, Ding S, Ma K, Jiang Y, Wang Y, Chen J, Wang Y, Kou Y, Fan X, Zhu X, Qin L, Qiu C, Simons M, Wei X, Yu L. SUMOylation Fine-Tunes Endothelial HEY1 in the Regulation of Angiogenesis. Circulation Research 2024, 134: 203-222. PMID: 38166414, PMCID: PMC10872267, DOI: 10.1161/circresaha.123.323398.Peer-Reviewed Original ResearchDNA-binding capabilityElectrophoretic mobility shift assaysEndothelial cell-specific expressionMobility shift assaysHairy/EnhancerCell-specific expressionPrimary human endothelial cellsNotch pathway componentsE-box promoter elementsEndothelial cellsRegulation of angiogenesisHelix familyPostnatal vascular growthHey1 functionsTranscriptional complexChromatin immunoprecipitationE3 ligaseRTK signalingEmbryonic developmentMatrigel plug assayPromoter elementsBioinformatics analysisShift assaysSUMOylationDNA binding
2023
Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension
Zhou X, Jiang Y, Wang Y, Fan L, Zhu Y, Chen Y, Wang Y, Zhu Y, Wang H, Pan Z, Li Z, Zhu X, Ren R, Ge Z, Lai D, Lai E, Chen T, Wang K, Liang P, Qin L, Liu C, Qiu C, Simons M, Yu L. Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension. Circulation Research 2023, 133: 508-531. PMID: 37589160, DOI: 10.1161/circresaha.122.321200.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionHypoxic pulmonary hypertensionPulmonary endothelial functionHuman pulmonary artery endothelial cellsPulmonary artery endothelial cellsPulmonary endotheliumArtery endothelial cellsEndothelial functionEndothelial cellsEndothelial mitochondriaSugen/hypoxia rat modelClinical specimensPulmonary endothelial dysfunctionHypoxia rat modelPulmonary arterial systemHypoxic stressVascular remodeling diseasePrevious clinical researchHuman embryonic stem cell-derived endothelial cellsMitochondrial oxygen consumption rateIntrinsic pathogenesisEndothelial dysfunctionExtracellular acidification rateHypoxic ratsPoor prognosis
2022
FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis
Zhu X, Qiu C, Wang Y, Jiang Y, Chen Y, Fan L, Ren R, Wang Y, Chen Y, Feng Y, Zhou X, Zhu Y, Ge Z, Lai D, Qin L, Simons M, Yu L. FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2202631119. PMID: 35733256, PMCID: PMC9245619, DOI: 10.1073/pnas.2202631119.Peer-Reviewed Original ResearchConceptsFGF receptor 1VEGFA/VEGFR2 signalingSmall ubiquitin-like modifier (SUMO) modificationSUMOylation-defective mutantReceptor complex formationTyrosine kinase activationVEGFA/VEGFR2Endothelial cellsFGF/FGFRRegulatory featuresEmbryonic developmentTissue homeostasisSUMOylationReversible SUMOylationKinase activationFibroblast growth factorBasic fibroblast growth factorFRS2αVascular developmentVEGFR2 signalingContradictory phenotypesEndothelial sproutingAngiogenic signalingFunctional significanceProangiogenic stimuliEndothelium‐derived lactate is required for pericyte function and blood–brain barrier maintenance
Lee H, Xu Y, Zhu X, Jang C, Choi W, Bae H, Wang W, He L, Jin S, Arany Z, Simons M. Endothelium‐derived lactate is required for pericyte function and blood–brain barrier maintenance. The EMBO Journal 2022, 41: e109890. PMID: 35243676, PMCID: PMC9058541, DOI: 10.15252/embj.2021109890.Peer-Reviewed Original ResearchConceptsGlucose transporter 1Blood-brain barrier breakdownBlood-brain barrier integrityBlood-brain barrier maintenanceMetabolic syndrome patientsLactate productionUseful therapeutic approachOral lactate administrationLactate administrationBarrier breakdownPericyte coverageSyndrome patientsPericyte functionTherapeutic approachesBarrier integrityVascular wallBrain vasculatureMice resultsBarrier maintenanceLactate supplementationEndothelial cellsTransporter 1LactatePericytesCell types
2019
Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition
Zhao W, Cao L, Ying H, Zhang W, Li D, Zhu X, Xue W, Wu S, Cao M, Fu C, Qi H, Hao Y, Tang YC, Qin J, Zhong TP, Lin X, Yu L, Li X, Li L, Wu D, Pan W. Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition. Cell Research 2019, 29: 895-910. PMID: 31501519, PMCID: PMC6889172, DOI: 10.1038/s41422-019-0229-5.Peer-Reviewed Original ResearchConceptsVEGFA stimulationEffects of VEGFAMutant zebrafishVascular morphogenesisVascular regressionSynthetase 2Bisphosphate availabilityMetabolic enzymesFOXO1 activationGenetic ablationPostnatal retinaAngiogenic endotheliumPhosphatidylinositolVEGFAPro-angiogenic factorsGrowth factorPathological conditionsVascular endothelial growth factorEndothelial cellsVessel regressionEndothelial growth factorTumor growthTumor modelNovel findingsZebrafish
2017
Nucleoside/nucleotide reverse transcriptase inhibitors attenuate angiogenesis and lymphangiogenesis by impairing receptor tyrosine kinases signalling in endothelial cells
Song L, Ding S, Ge Z, Zhu X, Qiu C, Wang Y, Lai E, Yang W, Sun Y, Chow S, Yu L. Nucleoside/nucleotide reverse transcriptase inhibitors attenuate angiogenesis and lymphangiogenesis by impairing receptor tyrosine kinases signalling in endothelial cells. British Journal Of Pharmacology 2017, 175: 1241-1259. PMID: 28910489, PMCID: PMC5866989, DOI: 10.1111/bph.14036.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinase internalizationExcessive ROS levelsConfocal immunofluorescence microscopyEndothelial cellsAntiretroviral therapyReceptor tyrosine kinasesMitochondrial DNA copy numberLymphatic endothelial cellsQuantitative real-time PCRMigration of ECsMitochondrial oxidative stressRTK endocytosisDNA copy numberProtein maturationRTK signalsEarly endosomesTube formation assaysTyrosine kinaseCardiovascular diseaseNucleoside/Blood vessel growthReal-time PCRFGFR1 pathwayCopy numberImmunofluorescence microscopyThe critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis
Qiu C, Wang Y, Zhao H, Qin L, Shi Y, Zhu X, Song L, Zhou X, Chen J, Zhou H, Zhang H, Tellides G, Min W, Yu L. The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis. Nature Communications 2017, 8: 15426. PMID: 28569748, PMCID: PMC5461500, DOI: 10.1038/ncomms15426.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriosclerosisCysteine EndopeptidasesDisease ProgressionDNAEndopeptidasesEndothelial CellsEndothelium, VascularGATA2 Transcription FactorHuman Umbilical Vein Endothelial CellsHumansInflammation MediatorsLeukocytesMaleMice, Inbred C57BLMice, KnockoutModels, BiologicalProtein BindingProtein StabilitySumoylationConceptsGraft arteriosclerosisEndothelial activationClinical graft rejectionConsequent endothelial dysfunctionNF-κB activityRole of SENP1Post-translational SUMOylationAllograft failureEndothelial dysfunctionGraft rejectionGraft endotheliumLeukocyte recruitmentVascular remodellingCardiovascular disordersNeointima formationNF-κBClinical researchDiminished inductionEndothelial cellsMajor causeAdhesion moleculesPotential involvementInflammationArteriosclerosisSENP1
2016
Nucleoside reverse transcriptase inhibitors attenuate angiogenesis and lymphangiogenesis by impairing receptor tyrosine kinases signaling in endothelial cells.
Song L, Zhu X, Qiu C, Qin L, Chow S, Yu L. Nucleoside reverse transcriptase inhibitors attenuate angiogenesis and lymphangiogenesis by impairing receptor tyrosine kinases signaling in endothelial cells. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.300.2.Peer-Reviewed Original ResearchAntiretroviral therapyReceptor tyrosine kinasesEndothelial cellsRole of ARTEndothelial mitochondrial dysfunctionHIV-positive patientsMicrovascular endothelial cellsVascular endothelial cellsAortic endothelial cellsNRTI treatmentTyrosine kinaseBlood vessel growthMicrovascular functionImmunodeficiency syndromeInhibitor administrationKaposi's sarcomaClinical challengeNoncommunicable diseasesNRTIsNotch1 pathwayAngiogenic pathwaysLymphangiogenic functionTumor angiogenesisLymphatic endothelial cellsReceptor signaling