2023
APOBEC-1 deletion enhances cisplatin-induced acute kidney injury
Guo X, Blanc V, Davidson N, Velazquez H, Chen T, Moledina D, Moeckel G, Safirstein R, Desir G. APOBEC-1 deletion enhances cisplatin-induced acute kidney injury. Scientific Reports 2023, 13: 22255. PMID: 38097707, PMCID: PMC10721635, DOI: 10.1038/s41598-023-49575-3.Peer-Reviewed Original ResearchPlasma 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 ResearchConceptsAcute pancreatitisSevere diseasePlasma renalase levelsAcute pancreatitis patientsSevere acute pancreatitisAcute pancreatitis modelPlasma renalaseRenalase levelsSignificant morbidityPancreatitis patientsPlasma levelsHealthy controlsPancreatitis modelPancreatitisPatientsPlasma samplesRenalaseDiseaseNonparametric statistical analysisSecretory proteinsMorbidityStatistical analysisMortalityLevels
2022
Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney
Chaurasia R, Salovey A, Guo X, Desir G, Vinetz JM. Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney. Frontiers In Cellular And Infection Microbiology 2022, 12: 926994. PMID: 35837473, PMCID: PMC9274288, DOI: 10.3389/fcimb.2022.926994.Peer-Reviewed Original ResearchConceptsLethal challenge infectionChallenge infectionBacterial loadC3H/HeJ miceKey target organClinical pathogenesisSevere leptospirosisOrgan infectionProtein immunizationHeJ miceSerovar CanicolaTarget organsAnimal modelsLeptospirosis pathogenesisCellular pathogenesisMicePathogenesisInfectionLeptospira interrogansVirulence factorsModifying proteinsImmunizationKidneyLeptospirosisLiverInhibition 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 ResearchConceptsPD-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 necrosis
2021
Renalase: 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 ResearchConceptsProsurvival 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
Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease
Landau SI, Guo X, Velazquez H, Torres R, Olson E, Garcia-Milian R, Moeckel GW, Desir GV, Safirstein R. Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease. Kidney International 2019, 95: 797-814. PMID: 30904067, PMCID: PMC6543531, DOI: 10.1016/j.kint.2018.11.042.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseKidney diseaseKidney injuryCisplatin-induced chronic kidney diseaseCisplatin-induced acute kidney injuryToll-like receptor 2Regulated necrosis pathwaysReversible kidney injuryAcute kidney injuryChronic kidney injuryProximal tubular damageKidney injury markersDoses of cisplatinEvidence of fibrosisMechanisms of progressionEffective chemotherapeutic agentWestern blot analysisFirst doseInjury markersIntraperitoneal cisplatinSignificant nephrotoxicityTubular damageKidney functionSecond doseCisplatin administration
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 model
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
Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD
Torres R, Velazquez H, Chang JJ, Levene MJ, Moeckel G, Desir GV, Safirstein R. Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD. Journal Of The American Society Of Nephrology 2015, 27: 1102-1112. PMID: 26303068, PMCID: PMC4814184, DOI: 10.1681/asn.2015010079.Peer-Reviewed Original ResearchConceptsAtubular glomeruliGlomerular capsuleRole of fibrosisModel of cisplatinNew mouse modelUseful morphologic informationMultiphoton microscopyTraditional histologic methodsRenal diseaseCisplatin therapyGlomerular volumePathologic changesRenal sectionsCKDMouse modelCisplatin effectCisplatin exposureImportant causeMild increaseCuboidal cellsHistologic methodsMorphologic informationFibrosisTherapyGlomeruli
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 ResearchConceptsKO 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
2013
Renalase in hypertension and kidney disease
Desir GV, Peixoto AJ. Renalase in hypertension and kidney disease. Nephrology Dialysis Transplantation 2013, 29: 22-28. PMID: 24137013, DOI: 10.1093/ndt/gft083.Peer-Reviewed Original ResearchRenalase regulates renal dopamine and phosphate metabolism
Sizova D, Velazquez H, Sampaio-Maia B, Quelhas-Santos J, Pestana M, Desir GV. Renalase regulates renal dopamine and phosphate metabolism. American Journal Of Physiology. Renal Physiology 2013, 305: f839-f844. PMID: 23863468, PMCID: PMC3761288, DOI: 10.1152/ajprenal.00616.2012.Peer-Reviewed Original ResearchConceptsRenal DA synthesisKO micePO4 excretionDA synthesisSodium-phosphate cotransporter Npt2aCatecholamine-degrading enzymeIntrinsic renal defectRenal dopamine synthesisWild-type miceKO mice showKnockout mouse modelDopa excretionRenalase deficiencySevere hypophosphatemiaRenal dopamineSerum PO4Urinary dopaminePhosphate excretionRegular dietDietary phosphateDopamine synthesisMouse modelMice showCompensatory increaseRenal defectsRenalase Protects against Ischemic AKI
Lee HT, Kim JY, Kim M, Wang P, Tang L, Baroni S, D’Agati V, Desir GV. Renalase Protects against Ischemic AKI. Journal Of The American Society Of Nephrology 2013, 24: 445-455. PMID: 23393318, PMCID: PMC3582209, DOI: 10.1681/asn.2012090943.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAdrenergic alpha-AntagonistsAnimalsApoptosisGene ExpressionHumansInflammation MediatorsIschemiaKidney Tubular Necrosis, AcuteMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMonoamine OxidaseNeutrophil InfiltrationNorepinephrinePhentolamineRecombinant ProteinsReperfusion InjuryRNA, MessengerConceptsRenal ischemia-reperfusion injuryIschemia-reperfusion injuryIschemic AKIWild-type miceReperfusion injuryCatecholamine levelsRenal tubular inflammationTreatment of AKIRenal ischemia reperfusionSham-operated micePlasma catecholamine levelsRenal tubular necrosisRecombinant human renalasePlasma renalaseTubular inflammationTubular necrosisIschemia reperfusionNE levelsPlasma catecholaminesMyocardial necrosisInflammatory responseProximal tubulesAKIRenalaseMice
2012
Human renalase: a review of its biology, function, and implications for hypertension
Desir GV, Wang L, Peixoto AJ. Human renalase: a review of its biology, function, and implications for hypertension. International Journal Of Cardiology Cardiovascular Risk And Prevention 2012, 6: 417-426. PMID: 23107895, DOI: 10.1016/j.jash.2012.09.002.Peer-Reviewed Original ResearchConceptsMechanism of actionBlood pressureIschemic acute kidney injuryEnd-stage renal diseaseAcute kidney injuryHeart transplant recipientsChronic kidney diseaseAmbulatory blood pressureGlomerular filtration rateTarget organ injuryNormal control subjectsEnzyme-linked immunosorbent assayCatecholamine-like substancesRenalase deficiencyRenalase levelsKidney injuryTransplant recipientsRenal dopamineAcute administrationChronic administrationRenal diseaseKidney diseaseControl subjectsFiltration ratePlasma levels
2011
Novel insights into the physiology of renalase and its role in hypertension and heart disease
Desir G. Novel insights into the physiology of renalase and its role in hypertension and heart disease. Pediatric Nephrology 2011, 27: 719-725. PMID: 21424526, DOI: 10.1007/s00467-011-1828-7.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseKidney diseaseResistant hypertensionSympathetic toneBlood pressureRecombinant renalaseSpontaneously Hypertensive Stroke-PronePlasma renalase levelsRenalase knockout mouseSystolic blood pressureModel of hypertensionPotent antihypertensive agentSevere cardiac hypertrophyRenalase deficiencyRenalase levelsRenal functionUrine catecholaminesEssential hypertensionSalt intakeStroke proneAntihypertensive agentsCatecholamine levelsRenal sodiumSingle dosePlasma levels