Xiaolong Zhu
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About
Research
Publications
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 prognosisAcetate 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 treatmentEndMTTGFDiseaseActivationInductionACSS2PDK4
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
2018
Subretinal Transplantation of Human Amniotic Epithelial Cells in the Treatment of Autoimmune Uveitis in Rats
Li J, Qiu C, Zhang Z, Yuan W, Ge Z, Tan B, Yang P, Liu J, Zhu X, Qiu C, Lai D, Guo L, Yu L. Subretinal Transplantation of Human Amniotic Epithelial Cells in the Treatment of Autoimmune Uveitis in Rats. Cell Transplantation 2018, 27: 1504-1514. PMID: 30168350, PMCID: PMC6180726, DOI: 10.1177/0963689718796196.Peer-Reviewed Original ResearchConceptsExperimental autoimmune uveitisHuman amniotic epithelial cellsT cell subsetsAutoimmune uveitisOcular inflammatory diseaseEAU ratsEnzyme-linked immunosorbent assayAmniotic epithelial cellsSubretinal transplantationInflammatory diseasesSubretinal injectionTherapeutic strategiesDay 0Current immunosuppressive regimensIL-10 levelsEpithelial cellsT regulatory (Treg) cellsImmune cell infiltrationSlit-lamp microscopyMonocyte chemoattractant proteinSerious side effectsInterphotoreceptor retinoid-binding proteinLocal cytokine environmentNovel therapeutic strategiesAlternative therapeutic strategiesTherapeutic effect of human amniotic epithelial cells in murine models of Hashimoto's thyroiditis and Systemic lupus erythematosus
Tan B, Yuan W, Li J, Yang P, Ge Z, Liu J, Qiu C, Zhu X, Qiu C, Lai D, Guo L, Wang L, Yu L. Therapeutic effect of human amniotic epithelial cells in murine models of Hashimoto's thyroiditis and Systemic lupus erythematosus. Cytotherapy 2018, 20: 1247-1258. PMID: 30174233, DOI: 10.1016/j.jcyt.2018.04.001.Peer-Reviewed Original ResearchConceptsExperimental autoimmune thyroiditisSystemic lupus erythematosusHuman amniotic epithelial cellsAnti-nuclear antibodiesSLE miceHashimoto's thyroiditisAutoimmune diseasesMurine modelAmniotic epithelial cellsEAT miceLupus erythematosusTherapeutic strategiesFemale CBA/J miceAnti-thyroid peroxidase antibodiesTh17/Treg cellsCBA/J miceAnti-thyroglobulin antibodiesAnti-dsDNA antibodiesEpithelial cellsNovel therapeutic strategiesNew therapeutic strategiesMRL-FasTreg cellsAutoimmune thyroiditisDifferent time points
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 microscopySUMOylation Negatively Regulates Angiogenesis by Targeting Endothelial NOTCH Signaling
Zhu X, Ding S, Qiu C, Shi Y, Song L, Wang Y, Wang Y, Li J, Wang Y, Sun Y, Qin L, Chen J, Simons M, Min W, Yu L. SUMOylation Negatively Regulates Angiogenesis by Targeting Endothelial NOTCH Signaling. Circulation Research 2017, 121: 636-649. PMID: 28760777, PMCID: PMC5581236, DOI: 10.1161/circresaha.117.310696.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBinding SitesCalcium-Binding ProteinsCells, CulturedCysteine EndopeptidasesEndopeptidasesHuman Umbilical Vein Endothelial CellsHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceNeovascularization, PhysiologicProtein BindingReceptors, NotchReceptors, Vascular Endothelial Growth FactorSignal TransductionSumoylationConceptsEndothelial NotchPost-translational SUMO modificationCell-cell interaction mechanismRole of SUMOylationNotch signal activationDual-luciferase assayCotranscriptional factorsRegulation of angiogenesisTissue patterningCell fateSUMO conjugationSUMO modificationSignal transductionVEGF receptor signalingSUMOylationImmunoprecipitation analysisRegulatory mechanismsPathway functionDLL4 stimulationBiological eventsReceptor signalingSignal activationCultured endothelial cellsAngiogenic signalingSENP1