2024
Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival
Zaman S, Gorelick F, Chrobrutskiy A, Chobrutskiy B, Desir G, Blanck G. Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival. Oncotarget 2024, 15: 550-561. PMID: 39102218, PMCID: PMC11299663, DOI: 10.18632/oncotarget.28633.Peer-Reviewed Original ResearchMeSH KeywordsAmidohydrolasesComplementarity Determining RegionsFemaleHumansMelanomaMonoamine OxidasePrognosisReceptors, Antigen, T-CellConceptsT cell receptorOverall survivalT cellsAssociated with improved overall survivalT-cell receptor CDR3sPromote T cell activationImproved overall survivalSurvival of melanomaPancreatic cancer patientsT cell activationT cell receptor recognitionTumor-residentTumor rejectionMelanoma patientsMelanoma growthMelanoma survivalImmune signature genesSurvival associationsCancer patientsMelanomaSignature genesAmino acid sequenceSurvivalPatientsExpression levels
2023
Plasma renalase levels are associated with the development of acute pancreatitis
Wang M, Weiss F, Guo X, Kolodecik T, Bewersdorf J, Laine L, Lerch M, Desir G, Gorelick F. Plasma renalase levels are associated with the development of acute pancreatitis. Pancreatology 2023, 23: 158-162. PMID: 36697349, DOI: 10.1016/j.pan.2023.01.001.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsHumansMiceMonoamine OxidasePancreatitisPrognosisSeverity of Illness IndexConceptsAcute pancreatitisSevere diseasePlasma renalase levelsAcute pancreatitis patientsSevere acute pancreatitisAcute pancreatitis modelPlasma renalaseRenalase levelsSignificant morbidityPancreatitis patientsPlasma levelsHealthy controlsPancreatitis modelPancreatitisPatientsPlasma samplesRenalaseDiseaseNonparametric statistical analysisSecretory proteinsMorbidityStatistical analysisMortalityLevels
2022
Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation
Wang M, Silva T, Toothaker JM, McCourt BT, Shugrue C, Desir G, Gorelick F, Konnikova L. Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation. Scientific Reports 2022, 12: 4953. PMID: 35322081, PMCID: PMC8943056, DOI: 10.1038/s41598-022-08817-6.Peer-Reviewed Original ResearchMeSH KeywordsChorionic VilliDeciduaFemaleHumansMonoamine OxidasePlacentaPlacentationPlasma Membrane Calcium-Transporting ATPasesPregnancyTrophoblastsConceptsPlacental tissuePlacental villiHofbauer cellsPlacental developmentEndogenous productionAnti-inflammatory milieuPotential roleHuman placental tissueFull-term placentaPlacental factorsFetal interfaceDecidual samplesPlacental functionChorionic plateImmunoreactive cellsPlacental samplesHuman gestationRenalaseBulk RNA sequencingHuman placentaPlacentaQuantification of immunohistochemistryProtein levelsTrophoblastTransmission of nutrientsAssociation of renalase with clinical outcomes in hospitalized patients with COVID-19
Safdar B, Wang M, Guo X, Cha C, Chun HJ, Deng Y, Dziura J, El-Khoury JM, Gorelick F, Ko AI, Lee AI, Safirstein R, Simonov M, Zhou B, Desir GV. Association of renalase with clinical outcomes in hospitalized patients with COVID-19. PLOS ONE 2022, 17: e0264178. PMID: 35259186, PMCID: PMC8903289, DOI: 10.1371/journal.pone.0264178.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsRenalase levelsIntensive care unit admissionHospitalized COVID-19 patientsMean age 64 yearsCOVID-19Cox proportional hazards modelCare unit admissionPrimary composite outcomeRetrospective cohort studyUse of vasopressorsSevere COVID-19IL-6 levelsAge 64 yearsRisk of deathCOVID-19 subjectsInitial disease severityProportional hazards modelCOVID-19 diseasePlasma renalaseUnit admissionICU admissionCohort studyComposite outcomeCytokine levelsInhibition of renalase drives tumour rejection by promoting T cell activation
Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansImmune Checkpoint InhibitorsImmunotherapyMelanomaMiceMonoamine OxidaseTumor MicroenvironmentConceptsPD-1 inhibitorsMurine melanoma modelMelanoma-bearing miceMelanoma modelTumor microenvironmentTumor rejectionCell death protein 1 (PD-1) inhibitorsAnti-PD-1 activityEnhanced T cell infiltrationT cell-dependent fashionMelanoma cellsMelanoma tumor regressionPreclinical melanoma modelsT cell infiltrationNatural killer cellsForkhead box P3Expression of IFNγWild-type miceProtein 1 inhibitorT cell activationTumor cell contentWild-type melanoma cellsCD4 cellsAdvanced melanomaAntibody treatmentKidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation
Guo X, Xu L, Velazquez H, Chen TM, Williams RM, Heller DA, Burtness B, Safirstein R, Desir GV. Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation. Journal Of The American Society Of Nephrology 2022, 33: 342-356. PMID: 34921111, PMCID: PMC8819981, DOI: 10.1681/asn.2021040439.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntineoplastic AgentsCell LineCisplatinCreatinineDisease Models, AnimalGene ExpressionGlomerular Filtration RateHepatitis A Virus Cellular Receptor 1HumansKidneyMiceMice, Inbred C57BLMice, KnockoutMonoamine OxidaseNanocapsulesPeptidesRenal Insufficiency, ChronicConceptsRenal proximal tubulesSingle-cell RNA sequencing analysisMesoscale nanoparticlesFirst doseCisplatin chemotherapyProximal tubulesAgonist peptideInduced Chronic Kidney DiseaseGenetic deletionNeck squamous cell carcinomaRNA sequencing analysisCisplatin-induced AKIKidney-targeted deliveryChronic kidney diseaseDevelopment of CKDSquamous cell carcinomaAdministration of cisplatinPlasma renalaseAdvanced headCell carcinomaInflammatory cytokinesKidney diseasePlasma creatinineSystemic administrationRegulated necrosisRENALASE: DISCOVERY, BIOLOGY, AND THERAPEUTIC APPLICATIONS.
Desir GV. RENALASE: DISCOVERY, BIOLOGY, AND THERAPEUTIC APPLICATIONS. Transactions Of The American Clinical And Climatological Association 2022, 132: 117-125. PMID: 36196172, PMCID: PMC9480547.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseStage renal diseaseCardiovascular complicationsOrgan survivalRenal diseaseAcute injuryKidney diseaseChronic injurySignificant burdenRenalaseStressful stimuliPeptide agonistsNicotinamide adenine dinucleotideMitochondrial functionInjuryEnergy metabolismDiseaseTherapeutic applicationsAdenine dinucleotideCellsComplicationsPathophysiologyAgonistsKidneyPancreas
2021
Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma
Gao Y, Wang M, Guo X, Hu J, Chen TM, Finn S, Lacy J, Kunstman JW, H. C, Bellin MD, Robert ME, Desir GV, Gorelick FS. Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma. PLOS ONE 2021, 16: e0250539. PMID: 34587190, PMCID: PMC8480607, DOI: 10.1371/journal.pone.0250539.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Pancreatic DuctalCase-Control StudiesFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMonoamine OxidaseNeoplasm GradingPancreatic NeoplasmsPrognosisProspective StudiesRetrospective StudiesSurvival AnalysisUp-RegulationYoung AdultConceptsPlasma renalase levelsBorderline resectable PDACRenalase levelsPDAC precursor lesionsOverall survivalPDAC tissuesTumor characteristicsResectable PDACChronic pancreatitisPrecursor lesionsNormal pancreasPancreatic ductal adenocarcinoma growthAdvanced tumor characteristicsVaried clinical stagesWorse tumor characteristicsNode-positive diseasePancreatic ductal adenocarcinomaNormal pancreatic headSpindle-shaped cellsPlasma renalaseRenalase expressionUnderwent resectionAbdominal traumaPancreatic headPositive diseaseRenalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease
Pointer TC, Gorelick FS, Desir GV. Renalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease. Cells 2021, 10: 2006. PMID: 34440775, PMCID: PMC8391834, DOI: 10.3390/cells10082006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGastrointestinal DiseasesGastrointestinal TractHumansMonoamine OxidaseProtein IsoformsSignal TransductionConceptsProsurvival effectAcute cerulein pancreatitisRole of renalaseAnti-inflammatory effectsDisease modelsAcute organ injuryRelevant clinical settingsShortens life expectancyPreclinical disease modelsCell survivalHuman cancer tissuesCancer cell survivalOrgan injuryAcute injuryPancreatic cancerIntestinal diseaseGastrointestinal diseasesRodent modelsCerulein pancreatitisSelect cancersCancer tissuesRenalaseClinical settingTherapeutic agentsExport transporters
2019
Elevated renalase levels in patients with acute coronary microvascular dysfunction – A possible biomarker for ischemia
Safdar B, Guo X, Johnson C, D'Onofrio G, Dziura J, Sinusas AJ, Testani J, Rao V, Desir G. Elevated renalase levels in patients with acute coronary microvascular dysfunction – A possible biomarker for ischemia. International Journal Of Cardiology 2019, 279: 155-161. PMID: 30630613, PMCID: PMC6482834, DOI: 10.1016/j.ijcard.2018.12.061.Peer-Reviewed Original ResearchConceptsCoronary microvascular dysfunctionFramingham risk scorePET/CTChest painInflammatory markersMicrovascular dysfunctionEmergency departmentRisk scoreRb-82 PET/CTElevated renalase levelsAcute chest painCoronary artery diseaseC-reactive proteinVascular endothelial growth factorAnti-inflammatory proteinTumor necrosis factorEndothelial growth factorAngina historyCMD diagnosisRenalase levelsHypertensive crisisED presentationsHemodynamic instabilityArtery diseaseHeart failure
2017
The serum protein renalase reduces injury in experimental pancreatitis
Kolodecik TR, Reed AM, Date K, Shugrue C, Patel V, Chung SL, Desir GV, Gorelick FS. The serum protein renalase reduces injury in experimental pancreatitis. Journal Of Biological Chemistry 2017, 292: 21047-21059. PMID: 29042438, PMCID: PMC5743078, DOI: 10.1074/jbc.m117.789776.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAnimalsAnti-Inflammatory Agents, Non-SteroidalBiomarkersCalcium SignalingCarbacholCell LineCeruletideEnzyme ActivationFluorescent Antibody Technique, IndirectGene Expression Regulation, EnzymologicHumansHypertensionLigandsMembrane Transport ModulatorsMiceMice, KnockoutMonoamine OxidasePancreasPancreatitisPlasma Membrane Calcium-Transporting ATPasesRecombinant Fusion ProteinsTaurolithocholic AcidConceptsRecombinant human renalaseAcute pancreatitisAcute injuryCell injuryAcinar cell injuryHuman acinar cellsCytosolic calcium levelsPlasma membrane calcium ATPasePancreatitis onsetIschemic injuryWT micePathological increaseHistological changesProtective effectSevere diseaseMurine modelMembrane calcium ATPasePancreatitisCalcium levelsExperimental pancreatitisBile acidsTissue damageRenalaseInjuryCerulein modelExtracellular renalase protects cells and organs by outside‐in signalling
Wang Y, Safirstein R, Velazquez H, Guo X, Hollander L, Chang J, Chen T, Mu J, Desir GV. Extracellular renalase protects cells and organs by outside‐in signalling. Journal Of Cellular And Molecular Medicine 2017, 21: 1260-1265. PMID: 28238213, PMCID: PMC5487909, DOI: 10.1111/jcmm.13062.Peer-Reviewed Original ResearchMeSH KeywordsBlood PressureCatecholaminesCytokinesHeart RateHumansKidneyMonoamine OxidaseNADPH OxidasesNeoplasmsOxidation-ReductionConceptsProtective effectNovel therapeutic strategiesCancer cell growthBlood pressureOrgan injuryJAK/STATHeart rateTherapeutic strategiesToxic injuryCytoprotective actionMitogen-activated protein kinase pathwayRenalaseTranslational opportunitiesTumor cellsCellular actionsProtein kinase BInitial reportProtein kinase pathwayInjuryKinase BOrgansKinase pathwayGrowth-related genesCell growthExtracellular renalase
2016
Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism
Hollander L, Guo X, Velazquez H, Chang J, Safirstein R, Kluger H, Cha C, Desir G. Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. Cancer Research 2016, 76: 3884-3894. PMID: 27197188, PMCID: PMC5031238, DOI: 10.1158/0008-5472.can-15-1524.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkers, TumorBlotting, WesternCase-Control StudiesCell CycleCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunoenzyme TechniquesMacrophagesMaleMelanomaMiceMice, Inbred C57BLMice, NudeMonoamine OxidaseNeoplasm StagingP38 Mitogen-Activated Protein KinasesPrognosisProto-Oncogene Proteins c-aktSignal TransductionSTAT3 Transcription FactorSurvival RateTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsTumor-associated macrophagesDisease-specific survivalManagement of melanomaPotential therapeutic implicationsCell cycle inhibitor p21Melanoma cell growthPI3K/AktMelanoma cell survivalCell growth arrestPathogenic rolePrimary melanomaToxic injuryMurine xenograftsTherapeutic implicationsTumor growthClinical specimensRenalaseBax activationTumor microenvironmentTumor cellsInhibitor p21Growth arrestSurvival factorElevated expressionMAPK pathwayA Remote Role for Renalase
Giordano FJ, Wang Y, Desir GV. A Remote Role for Renalase. EBioMedicine 2016, 9: 27-28. PMID: 27374133, PMCID: PMC4972559, DOI: 10.1016/j.ebiom.2016.06.034.Peer-Reviewed Original ResearchInhibition of renalase expression and signaling has antitumor activity in pancreatic cancer
Guo X, Hollander L, MacPherson D, Wang L, Velazquez H, Chang J, Safirstein R, Cha C, Gorelick F, Desir GV. Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer. Scientific Reports 2016, 6: 22996. PMID: 26972355, PMCID: PMC4789641, DOI: 10.1038/srep22996.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibodiesApoptosisCarcinoma, Pancreatic DuctalCell Cycle CheckpointsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateMaleMice, NudeMiddle AgedMonoamine OxidasePancreatic NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionXenograft Model Antitumor AssaysConceptsRenalase expressionPancreatic cancerPancreatic ductal adenocarcinoma growthCohort of patientsPancreatic cancer tissuesPancreatic ductal adenocarcinomaPancreatic ductal adenocarcinoma cellsXenograft mouse modelAttractive therapeutic targetDuctal adenocarcinoma cellsTumor cell apoptosisOverall survivalPathogenic roleCell cycle arrestDuctal adenocarcinomaPrognostic makerTumor massMouse modelTherapeutic targetCellular injuryCancer tissuesRenalaseCancerAdenocarcinoma cellsGrowth factor
2015
Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis
Qi C, Wang L, Zhang M, Shao X, Chang X, Fan Z, Cao Q, Mou S, Wang Q, Yan Y, Desir G, Ni Z. Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis. PLOS ONE 2015, 10: e0139627. PMID: 26431044, PMCID: PMC4592194, DOI: 10.1371/journal.pone.0139627.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkersCase-Control StudiesCross-Sectional StudiesDisease ProgressionFemaleHumansLupus NephritisMaleMiddle AgedMonoamine OxidaseConceptsSerum renalase levelsActive lupus nephritisLupus nephritisDisease activityProliferative lupus nephritisRenalase levelsLN patientsSystemic lupus erythematosusStandard therapyDisease progressionHealthy controlsActive LN patientsInactive lupus nephritisProliferative LN patientsSLEDAI-2KSLE disease activityUrine protein excretionKidneys of patientsCross-sectional studyExpression of renalaseCytokine-like proteinLupus erythematosusSerious complicationsProtein excretionSerum renalaseIdentification of a Receptor for Extracellular Renalase
Wang L, Velazquez H, Chang J, Safirstein R, Desir GV. Identification of a Receptor for Extracellular Renalase. PLOS ONE 2015, 10: e0122932. PMID: 25906147, PMCID: PMC4407985, DOI: 10.1371/journal.pone.0122932.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryCell LineCytoprotectionDown-RegulationEpidermal Growth FactorEssential HypertensionHumansHypertensionMitogen-Activated Protein KinasesMonoamine OxidasePlasma Membrane Calcium-Transporting ATPasesPolymorphism, Single NucleotideProtein Interaction Domains and MotifsSignal TransductionConceptsAcute kidney injuryIntrinsic enzymatic activityMAPK signalingExtracellular renalaseHuman proximal tubular cell line HK-2Enzymatic activitySingle nucleotide gene polymorphismsAcute ischemic kidneyWild-type miceProtein-protein interactionsPlasma membrane ATPaseKidney injuryIschemic kidneyEssential hypertensionIschemic injuryCardiac injuryPMCA4b expressionRecombinant renalaseEpidermal growth factorType miceCardiac hypertrophyHK-2Control studyGene polymorphismsCell signaling
2014
Renalase regulates peripheral and central dopaminergic activities
Quelhas-Santos J, Serrão MP, Soares-Silva I, Fernandes-Cerqueira C, Simões-Silva L, Pinho MJ, Remião F, Sampaio-Maia B, Desir GV, Pestana M. Renalase regulates peripheral and central dopaminergic activities. American Journal Of Physiology. Renal Physiology 2014, 308: f84-f91. PMID: 25411385, PMCID: PMC4338928, DOI: 10.1152/ajprenal.00274.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainDopamineDopaminergic NeuronsJejunumKidneyMaleMice, Inbred C57BLMice, KnockoutMonoamine OxidaseConceptsKO miceUrinary excretionPlasma levelsDopaminergic activityIncreased Plasma LevelsPeripheral dopaminergic activityUrine catecholamine levelsRenal dopaminergic systemCentral dopaminergic activityL-type amino acid transporterWild-type miceAmino acid decarboxylase activityKnockout mouse modelRenalase deficiencyCatecholamine levelsDA outputUrinary dopamineAADC activityDopaminergic systemRenal cortexMouse modelDOPA ratioVivo administrationOverexpression of LAT1Amino acid transportersRenalase
Guo X, Wang L, Velazquez H, Safirstein R, Desir GV. Renalase. Current Opinion In Nephrology & Hypertension 2014, 23: 513-518. PMID: 24992568, PMCID: PMC4383282, DOI: 10.1097/mnh.0000000000000044.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsEnzymatic functionType 1 diabetesMitogen-activated protein kinase pathwayNucleotide polymorphismsProtein kinase BProtein kinase pathwayCellular actionsPlasma membraneKinase pathwayKinase BPotential therapeutic utilityCertain single nucleotide polymorphismsEnzymatic propertiesIschemic strokeImmune modulatorsRenalase geneTherapeutic utilityCytoprotective effectsClinical implicationsRenalaseConsistent associationPotential roleDiabetesCytokinesRenalase Prevents AKI Independent of Amine Oxidase Activity
Wang L, Velazquez H, Moeckel G, Chang J, Ham A, Lee HT, Safirstein R, Desir GV. Renalase Prevents AKI Independent of Amine Oxidase Activity. Journal Of The American Society Of Nephrology 2014, 25: 1226-1235. PMID: 24511138, PMCID: PMC4033373, DOI: 10.1681/asn.2013060665.Peer-Reviewed Original ResearchConceptsIschemic injuryCatecholamine levelsRecombinant renalaseAmine oxidase activityHuman proximal tubular cellsCisplatin-induced AKITreatment of AKIWild-type miceHK-2 cellsProximal tubular cellsOxidase activityKidney injuryRenal injuryC-Jun N-terminal kinaseExtracellular signal-regulated kinaseP38 mitogen-activated protein kinaseToxic injuryRenalase proteinTubular cellsSignal-regulated kinaseIntracellular signaling cascadesRenalaseInjuryMitogen-activated protein kinaseN-terminal kinase