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
SUMOylation 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