2023
Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury
Wen Y, Su E, Xu L, Menez S, Moledina D, Obeid W, Palevsky P, Mansour S, Devarajan P, Cantley L, Cahan P, Parikh C, Project K, Injury T. Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury. Science Translational Medicine 2023, 15: eade7287. PMID: 38091407, PMCID: PMC11405121, DOI: 10.1126/scitranslmed.ade7287.Peer-Reviewed Original ResearchThe ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events
Menez S, Wen Y, Xu L, Moledina D, Thiessen-Philbrook H, Hu D, Obeid W, Bhatraju P, Ikizler T, Siew E, Chinchilli V, Garg A, Go A, Liu K, Kaufman J, Kimmel P, Himmelfarb J, Coca S, Cantley L, Parikh C. The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events. Kidney International 2023, 104: 1194-1205. PMID: 37652206, PMCID: PMC10840723, DOI: 10.1016/j.kint.2023.08.007.Peer-Reviewed Original ResearchConceptsMajor adverse kidney eventsUEGF/CrUrinary epidermal growth factorAdverse kidney eventsChronic kidney diseaseEpidermal growth factorKidney eventsKidney failureEGF expressionUrinary EGF/CrAcute Kidney Injury studyGrowth factorIschemia-reperfusion injuryProportional hazards regressionTubular healthKidney atrophyObservational cohortHospitalized participantsTubular functionClinical findingsHazards regressionKidney diseaseClinical variablesProgressive atrophyUrinary EGFLongitudinal biomarkers and kidney disease progression after acute kidney injury
Wen Y, Xu L, Melchinger I, Thiessen-Philbrook H, Moledina D, Coca S, Hsu C, Go A, Liu K, Siew E, Ikizler T, Chinchilli V, Kaufman J, Kimmel P, Himmelfarb J, Cantley L, Parikh C, Consortium T. Longitudinal biomarkers and kidney disease progression after acute kidney injury. JCI Insight 2023, 8: e167731. PMID: 36951957, PMCID: PMC10243801, DOI: 10.1172/jci.insight.167731.Peer-Reviewed Original ResearchConceptsAcute kidney injuryIschemic reperfusion injuryKidney disease progressionKidney injuryTubular healthDisease progressionChronic kidney disease (CKD) incidenceCox proportional hazards regressionMurine acute kidney injuryKidney disease incidenceUrine KIM-1Proportional hazards regressionCKD progressionCKD transitionUrine uromodulinIncident CKDComposite outcomeKidney atrophyProspective cohortReperfusion injuryHazards regressionKIM-1Prognostic valueMCP-1Initial insult
2022
Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis
Melchinger H, Calderon-Gutierrez F, Obeid W, Xu L, Shaw MM, Luciano RL, Kuperman M, Moeckel GW, Kashgarian M, Wilson FP, Parikh CR, Moledina DG. Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis. Clinical Journal Of The American Society Of Nephrology 2022, 17: 1284-1292. PMID: 35948365, PMCID: PMC9625093, DOI: 10.2215/cjn.04360422.Peer-Reviewed Original ResearchConceptsInterstitial fibrosis/tubular atrophyUrine uromodulinTubular atrophyThick ascending limbUrine albuminSerum creatinineKidney biopsyTubulointerstitial fibrosisMultivariable linear regression modelsTime of biopsyKidney's thick ascending limbAcademic medical centerHuman kidney biopsiesKidney tubulointerstitial fibrosisTubular healthMultivariable analysisHistologic featuresHistologic findingsHistologic changesKidney fibrosisIndependent associationFibrotic modelMultivariable modelMedical CenterMurine modelImmune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition
Xu L, Guo J, Moledina DG, Cantley LG. Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition. Nature Communications 2022, 13: 4892. PMID: 35986026, PMCID: PMC9391331, DOI: 10.1038/s41467-022-32634-0.Peer-Reviewed Original ResearchConceptsAcute kidney injuryKidney injuryT cellsChronic kidney disease transitionIschemia-reperfusion kidney injuryKidney disease transitionChronic kidney diseaseDepletion of neutrophilsGlomerular filtration rateT cell recruitmentTubular cell lossMacrophage persistenceProinflammatory neutrophilsTubule damageKidney atrophyContralateral kidneyNeutrophil numbersContralateral nephrectomyKidney diseaseTubule atrophyFiltration rateCell recruitmentMore macrophagesDay 14Day 5Arginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration
Shin NS, Marlier A, Xu L, Doilicho N, Linberg D, Guo J, Cantley LG. Arginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration. Journal Of The American Society Of Nephrology 2022, 33: 1077-1086. PMID: 35577558, PMCID: PMC9161787, DOI: 10.1681/asn.2021121548.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryTubular cell proliferationArginase-1Contralateral nephrectomyRenal repairFl/Littermate controlsTubular cellsReceptor 1GM-CSFRenal tubular cell proliferationRenal tubule regenerationMacrophage scavenger receptor 1Mannose receptor 1Cell proliferative responsesCell proliferationScavenger receptor 1Coculture of macrophagesDead cell debrisKidney injuryKidney repairRenal responseProinflammatory activationTubule regenerationMouse survivalKidney-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
Biomarkers of inflammation and repair in kidney disease progression
Puthumana J, Thiessen-Philbrook H, Xu L, Coca SG, Garg AX, Himmelfarb J, Bhatraju PK, Ikizler T, Siew E, Ware LB, Liu KD, Go AS, Kaufman JS, Kimmel PL, Chinchilli VM, Cantley L, Parikh CR. Biomarkers of inflammation and repair in kidney disease progression. Journal Of Clinical Investigation 2021, 131 PMID: 33290282, PMCID: PMC7843225, DOI: 10.1172/jci139927.Peer-Reviewed Original ResearchConceptsKidney disease progressionComposite kidney outcomeChronic kidney diseaseDisease progressionEGFR declineKidney outcomesRenal atrophyMouse modelMonocyte chemoattractant protein-1CHI3L1 mRNA expressionComposite renal outcomeGreater eGFR declineIntroductionAcute kidney injuryProspective cohort studyGlomerular filtration rateBiomarkers of inflammationProgressive renal fibrosisYKL-40 levelsChemoattractant protein-1Traditional clinical variablesLong-term progressionLoop of HenleMultimarker scoreRenal outcomesKidney injury
2019
Tubular GM-CSF Promotes Late MCP-1/CCR2-Mediated Fibrosis and Inflammation after Ischemia/Reperfusion Injury
Xu L, Sharkey D, Cantley LG. Tubular GM-CSF Promotes Late MCP-1/CCR2-Mediated Fibrosis and Inflammation after Ischemia/Reperfusion Injury. Journal Of The American Society Of Nephrology 2019, 30: 1825-1840. PMID: 31315923, PMCID: PMC6779361, DOI: 10.1681/asn.2019010068.Peer-Reviewed Original ResearchConceptsIschemia/reperfusion injuryWild-type miceTubular cellsTubular injuryReperfusion injuryImmune cellsKidney ischemia/reperfusion injuryUnilateral ischemia/reperfusion injuryMCP-1/CCR2Monocyte chemoattractant protein-1Initial kidney damageInjured tubular cellsKidney 14 daysKidney injury markersProgressive interstitial fibrosisProfibrotic growth factorsChemoattractant protein-1MCP-1 receptorGranulocyte-macrophage colony-stimulating factorRenal tubular cellsNumber of macrophagesTime of repairColony-stimulating factorCoculture of macrophagesMacrophages persistFolate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy
Xu L, Yang H. Folate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy. Methods In Molecular Biology 2019, 1974: 393-408. PMID: 31099016, DOI: 10.1007/978-1-4939-9220-1_26.BooksConceptsGene therapyGene delivery systemsNeck cancer gene therapyCancer gene therapyDelivery systemNanoparticle carriersGene deliveryDendrimer nanoparticlesHigh biocompatibilityGene transfectionKnockdown efficiencyTumor targetingSuitable platformFolic acidIRDye 800CWSustained retentionGeneration 4DendrimersNanoparticlesBioimagingCarriersBiocompatibilityHereinPlatformPlasmid
2017
Breast Regression Protein–39/Chitinase 3–Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of Myofibroblasts
Montgomery TA, Xu L, Mason S, Chinnadurai A, Lee CG, Elias JA, Cantley LG. Breast Regression Protein–39/Chitinase 3–Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of Myofibroblasts. Journal Of The American Society Of Nephrology 2017, 28: 3218-3226. PMID: 28679671, PMCID: PMC5661290, DOI: 10.1681/asn.2017010110.Peer-Reviewed Original ResearchConceptsBRP-39Kidney injuryKidney repairChitinase 3Unilateral ischemia-reperfusion injuryBreast regression protein 39Kidney 14 daysPromotes Renal FibrosisRobust inflammatory infiltrateSevere interstitial fibrosisIschemia-reperfusion injuryActivation of myofibroblastsTubular cell survivalProfibrotic growth factorsWild-type miceIL-13 receptorAnalysis of macrophagesMacrophage persistenceTubular injuryInflammatory infiltrateProfibrotic markersInterstitial fibrosisRenal fibrosisMyofibroblast accumulationProfibrotic signalingFolic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery
Xu L, Yeudall WA, Yang H. Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery. Acta Biomaterialia 2017, 57: 251-261. PMID: 28438704, PMCID: PMC5555737, DOI: 10.1016/j.actbio.2017.04.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Squamous CellCell Line, TumorDendrimersFemaleFolic AcidGene Transfer TechniquesHead and Neck NeoplasmsHumansMiceMice, NudeNeoplasm ProteinsNeovascularization, PathologicPolyaminesRNA, Small InterferingVascular Endothelial Growth Factor AXenograft Model Antitumor AssaysConceptsHigh tumor uptakeNeck squamous cell carcinomaSquamous cell carcinomaTumor uptakeCell carcinomaLocal deliveryRegimen studiesNeck squamous cancer cellsPronounced tumor suppressionTumor size reductionVascular endothelial growth factorSquamous cancer cellsTumor mouse modelEndothelial growth factorXenograft tumor modelEnhanced tumor uptakeTumor suppressionTumor inhibition effectCommon cancerMicrovessel countImaging assessmentTherapeutic modalitiesMouse modelCD31 stainingTreatment groups
2014
Semi-Interpenetrating Network (sIPN) Co-Electrospun Gelatin/Insulin Fiber Formulation for Transbuccal Insulin Delivery
Xu L, Sheybani N, Ren S, Bowlin GL, Yeudall WA, Yang H. Semi-Interpenetrating Network (sIPN) Co-Electrospun Gelatin/Insulin Fiber Formulation for Transbuccal Insulin Delivery. Pharmaceutical Research 2014, 32: 275-285. PMID: 25030186, DOI: 10.1007/s11095-014-1461-9.Peer-Reviewed Original ResearchConceptsMechanical propertiesPEG-DAModerate degradation rateDegradation ratePolyethylene glycol diacrylateScaffold formulationsFiber formulationsGlycol diacrylateSuitable formulationRelease kineticsSignificant enhancementSIPNsEosin YDrug deliveryInsulin deliveryNew formulationFormulationPermeabilityPropertiesCytocompatibilityFibersOil Red O stainingTransbuccal drug deliveryMethodsGelatinRed O stainingClick Hybridization of Immune Cells and Polyamidoamine Dendrimers
Xu L, Zolotarskaya OY, Yeudall WA, Yang H. Click Hybridization of Immune Cells and Polyamidoamine Dendrimers. Advanced Healthcare Materials 2014, 3: 1430-1438. PMID: 24574321, PMCID: PMC4133313, DOI: 10.1002/adhm.201300515.Peer-Reviewed Original ResearchCholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor 4α
Shi X, Cheng Q, Xu L, Yan J, Jiang M, He J, Xu M, Stefanovic-Racic M, Sipula I, O'Doherty RM, Ren S, Xie W. Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor 4α. Molecular And Cellular Biology 2014, 34: 485-497. PMID: 24277929, PMCID: PMC3911511, DOI: 10.1128/mcb.01094-13.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBlotting, WesternCarcinoma, HepatocellularCell Line, TumorCell NucleusCells, CulturedCholesterol EstersCoenzyme A LigasesColforsinDiet, High-FatGene ExpressionGluconeogenesisGlucoseHepatocyte Nuclear Factor 4HumansInsulin ResistanceMiceMice, Inbred C57BLMice, ObeseMice, TransgenicObesityReverse Transcriptase Polymerase Chain ReactionSulfotransferasesConceptsDiet-induced obesityHepatocyte nuclear factor 4αNuclear factor 4αCholesterol sulfateLeptin-deficient miceTreatment of micePotential therapeutic targetPotential therapeutic agentExpression of SULT2B1bMetabolic abnormalitiesObese miceMetabolic disordersImportant metabolic regulatorGlucose metabolismTherapeutic targetTransgenic miceFed stateHepatic gluconeogenesisTherapeutic agentsMiceTransgenic overexpressionSULT2B1bMetabolic regulatorFunctional homeostasisInhibits gluconeogenesis
2012
5-Cholesten-3β,25-Diol 3-Sulfate Decreases Lipid Accumulation in Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model
Xu L, Kim JK, Bai Q, Zhang X, Kakiyama G, Min HK, Sanyal AJ, Pandak WM, Ren S. 5-Cholesten-3β,25-Diol 3-Sulfate Decreases Lipid Accumulation in Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model. Molecular Pharmacology 2012, 83: 648-658. PMID: 23258548, PMCID: PMC3583496, DOI: 10.1124/mol.112.081505.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl-CoA CarboxylaseAcetyltransferasesAnimalsCholesterol EstersDiet, High-FatFas ReceptorFatty AcidsFatty LiverFemaleGene ExpressionGlucose Tolerance TestGlycerol-3-Phosphate O-AcyltransferaseHydroxycholesterolsInflammationInsulinInsulin ResistanceInterleukin-1alphaInterleukin-1betaLipid MetabolismLipidsLiverMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseSignal TransductionSterol Regulatory Element Binding Protein 1Tumor Necrosis Factor-alphaConceptsNonalcoholic fatty liver diseaseHigh-fat dietLong-term treatmentAcute treatmentTolerance testLipid accumulationMouse modelDiet-induced NAFLD mouse modelNonalcoholic fatty liver disease (NAFLD) mouse modelSREBP-1cLipid homeostasisFatty liver diseaseLiver X receptor αNAFLD mouse modelGlucose tolerance testSerum lipid levelsInsulin tolerance testHepatic lipid accumulationDisease mouse modelDecreases lipid accumulationTumor necrosis factorLipid-induced inflammationAcetyl-CoA carboxylase 1X receptor αSREBP-1c expressionCholesterol metabolite, 5-cholesten-3β-25-diol-3-sulfate, promotes hepatic proliferation in mice
Zhang X, Bai Q, Kakiyama G, Xu L, Kim JK, Pandak WM, Ren S. Cholesterol metabolite, 5-cholesten-3β-25-diol-3-sulfate, promotes hepatic proliferation in mice. The Journal Of Steroid Biochemistry And Molecular Biology 2012, 132: 262-270. PMID: 22732306, PMCID: PMC3463675, DOI: 10.1016/j.jsbmb.2012.06.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell CycleCell ProliferationCholesterolCholesterol EstersDNA ReplicationGene Expression RegulationHydrocarbons, FluorinatedHydroxycholesterolsLiverLiver X ReceptorsMiceMice, Inbred C57BLOrphan Nuclear ReceptorsSignal TransductionSulfonamidesSulfotransferasesTissue DistributionUp-RegulationConceptsLiver X receptorHepatic proliferationSynthetic LXR agonist T0901317LXR agonist T0901317PCNA labeling indexDose-dependent mannerSuppresses cell proliferationOxysterol sulfationOxysterol sulfotransferaseProliferation gene expressionAgonist T0901317Cholesterol metabolitesLabeling indexEndogenous ligandLiver proliferationX receptorHepatic DNA replicationHepatocyte proliferationSREBP-1cNovel regulatory pathwayPCR arrayCell proliferationAdministrationPotent regulatorOxysterolsCytosolic sulfotransferase 2B1b promotes hepatocyte proliferation gene expression in vivo and in vitro
Zhang X, Bai Q, Xu L, Kakiyama G, Pandak WM, Zhang Z, Ren S. Cytosolic sulfotransferase 2B1b promotes hepatocyte proliferation gene expression in vivo and in vitro. AJP Gastrointestinal And Liver Physiology 2012, 303: g344-g355. PMID: 22679001, PMCID: PMC3423104, DOI: 10.1152/ajpgi.00403.2011.Peer-Reviewed Original ResearchConceptsLiver X receptorMouse liver tissueLiver tissueSulfotransferase 2B1bLiver proliferationPCNA-positive cellsPrimary rat hepatocytesCell nuclear antigenOxysterol sulfotransferaseWestern blot analysisCell cycle regulatory gene expressionProliferation gene expressionTime-dependent mannerGene expressionC57BL/6 miceQuantitative real-time PCRReal-time PCRLXR activationDouble immunofluorescenceLabeling indexSelective cholesterolAntiproliferative factorPCNA expressionLipid metabolismIncreased expressionOxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor/sterol regulatory element binding protein–1c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver disease
Bai Q, Zhang X, Xu L, Kakiyama G, Heuman D, Sanyal A, Pandak WM, Yin L, Xie W, Ren S. Oxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor/sterol regulatory element binding protein–1c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver disease. Metabolism 2012, 61: 836-845. PMID: 22225954, PMCID: PMC3342481, DOI: 10.1016/j.metabol.2011.11.014.Peer-Reviewed Original ResearchConceptsHepatic lipid levelsOxysterol sulfationSULT2B1b expressionLipid levelsLipid metabolismNonalcoholic fatty liver diseaseWestern blotFatty liver diseaseLiver X receptor αHigh-cholesterol dietReal-time reverse transcriptase-polymerase chain reactionHigh-fat dietReverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionAcetyl-CoA carboxylase 1X receptor αImportant endogenous regulatorLiver diseaseTotal cholesterolHepatic lipidsHepatic steatosisFatty acid synthasePolymerase chain reactionSterol regulatory element-binding proteinLung tissue
2009
StAR Overexpression Decreases Serum and Tissue Lipids in Apolipoprotein E‐deficient Mice
Ning Y, Xu L, Ren S, Pandak WM, Chen S, Yin L. StAR Overexpression Decreases Serum and Tissue Lipids in Apolipoprotein E‐deficient Mice. Lipids 2009, 44: 511-519. PMID: 19373502, PMCID: PMC2911774, DOI: 10.1007/s11745-009-3299-1.Peer-Reviewed Original ResearchConceptsDeficient miceApolipoprotein ESerum HDL cholesterolSerum total cholesterolTreatment of dyslipidemiaPossible therapeutic roleSudan IV stainingMonths of ageNeutral lipid stainingSteroidogenic acute regulatory proteinDecreases SerumHDL cholesterolTotal cholesterolTriglyceride levelsAcute regulatory proteinTherapeutic roleStAR protein expressionCholesterol metabolismAnimal modelsAortic wallTissue lipidsLipid accumulationMiceRecombinant cytomegalovirusesLipid homeostasis