2024
Adamts1 and Cyst Expansion in Polycystic Kidney Disease.
Kakade V, Akman Z, Motrapu M, Cassini M, Xu L, Moeckel G, Somlo S, Cantley L. Adamts1 and Cyst Expansion in Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2024 PMID: 39514301, DOI: 10.1681/asn.0000000557.Peer-Reviewed Original ResearchAutosomal dominant polycystic kidney diseasePolycystic kidney diseaseKidney diseaseLoss of Pkd1Cyst growthInterstitial macrophage accumulationDominant polycystic kidney diseaseInterstitial mononuclear cellsReduced cyst growthDetectable phenotypeMembrane remodelingMotif 1Progressive cyst growthIsoforms of versicanSimultaneous deletionPKD2 geneTubular basement membraneDisintegrin and metalloproteinaseRNA sequencingBasement membrane remodelingPKD1Thrombospondin motifs 1Cystic enlargementMacrophage accumulationCystic dilatationMyofibroblast-Macrophage Cross-Talk Supports Proliferative Tubule Repair after Kidney Injury
Bharathan B, Xu L, Guo J, Cantley L. Myofibroblast-Macrophage Cross-Talk Supports Proliferative Tubule Repair after Kidney Injury. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.20249phzkecs. DOI: 10.1681/asn.20249phzkecs.Peer-Reviewed Original ResearchVCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition
Melchinger I, Guo K, Li X, Guo J, Cantley L, Xu L. VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition. American Journal Of Physiology. Renal Physiology 2024, 327: f610-f622. PMID: 39116349, PMCID: PMC11483080, DOI: 10.1152/ajprenal.00076.2024.Peer-Reviewed Original ResearchAcute kidney injuryChronic kidney diseaseVCAM-1 expressionProximal tubule cellsVCAM-1Tubule cellsKidney Precision Medicine ProjectProinflammatory cytokinesAcute kidney injury to chronic kidney diseaseModel of chronic kidney diseaseExpression of vascular cell adhesion protein 1Cell adhesion pathwaysInflammatory response to injuryInjured proximal tubule cellsVascular cell adhesion protein 1Mouse model of chronic kidney diseaseRisk of progressionChronic kidney disease transitionIncreased immune cell adhesionVCAM-1-positive cellsOverexpression of VCAM-1Inhibition of NF-kB signalingActivation of NF-kBImmune cell adhesionSingle-cell transcriptome analysis
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 necrosisCharacterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury
Shin NS, Marlier A, Xu L, Lam T, Cantley LG, Guo JK. Characterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury. American Journal Of Physiology. Renal Physiology 2022, 322: f322-f334. PMID: 35100823, PMCID: PMC8897010, DOI: 10.1152/ajprenal.00284.2021.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryCast formationGlomerular filtration rateTubular cast formationUrine 24 hDetached epithelial cellsDead cell debrisRenal recoveryRenal functionFiltration rateS3 tubulesTubular castsTubular cellsTubular nucleiKidney sectionsOuter medullaTrypsin levelsEntire nephronRenal tubular castsFuture interventionsInjurySelective lossTubule segmentsEpithelial cellsKidney
2021
The Role of Myeloid Cells in Acute Kidney Injury and Kidney Repair
Xu L. The Role of Myeloid Cells in Acute Kidney Injury and Kidney Repair. Kidney360 2021, 2: 1852-1864. PMID: 35372990, PMCID: PMC8785849, DOI: 10.34067/kid.0000672021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsBiomarkers 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
Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery
Xu L, Cooper RC, Wang J, Yeudall WA, Yang H. Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery. ACS Biomaterials Science & Engineering 2017, 3: 1641-1653. PMID: 29147682, PMCID: PMC5683721, DOI: 10.1021/acsbiomaterials.7b00166.Peer-Reviewed Original ResearchStrain-promoted azide-alkyne cycloadditionAzide-alkyne cycloadditionDegree of PEGylationCross-linked networkDBCO groupsBioorthogonal chemistryDendrimer generationPEG spacerDrug deliveryChain lengthGeneration 4.0Sustained releaseHigh cytocompatibilityLocal drug deliveryPEG-BALoading densityDibenzocyclooctyneAnticancer drugsHydrogelsPhysical propertiesStructural parametersDendrimersBisazideChemistryCycloadditionBreast 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 groupsFolate-mediated chemotherapy and diagnostics: An updated review and outlook
Xu L, Bai Q, Zhang X, Yang H. Folate-mediated chemotherapy and diagnostics: An updated review and outlook. Journal Of Controlled Release 2017, 252: 73-82. PMID: 28235591, PMCID: PMC5479736, DOI: 10.1016/j.jconrel.2017.02.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsFolate receptorCellular uptake mechanismVivo applicationsDiagnostic agentsNanomedicineNanoprobeTremendous effortsNanoparticlesMajor challengeClinical applicationAdministration routeDiagnosticsChemotherapyApplicationsHuman cancersLatest developmentsUptake mechanismPharmacokineticsConcise reviewRouteReview
2016
Folic acid-decorated polyamidoamine dendrimer mediates selective uptake and high expression of genes in head and neck cancer cells
Xu L, Kittrell S, Yeudall WA, Yang H. Folic acid-decorated polyamidoamine dendrimer mediates selective uptake and high expression of genes in head and neck cancer cells. Nanomedicine 2016, 11: 2959-2973. PMID: 27781559, PMCID: PMC5144492, DOI: 10.2217/nnm-2016-0244.Peer-Reviewed Original ResearchConceptsNeck cancer cellsCancer cellsFR-dependent mannerEnhanced gene expressionGene expressionSame binding siteCellular uptakeGenesDelivery of genesBinding sitesHigh expressionFree FASuitable vectorPlasmidDNA plasmidsCellsTransfection resultsExpressionTransfection efficiencySelective uptakeUptakeFolate receptorHigh levelsVectorFA