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 EGFIdentification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis
Moledina D, Obeid W, Smith R, Rosales I, Sise M, Moeckel G, Kashgarian M, Kuperman M, Campbell K, Lefferts S, Meliambro K, Bitzer M, Perazella M, Luciano R, Pober J, Cantley L, Colvin R, Wilson F, Parikh C. Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. Journal Of Clinical Investigation 2023, 133: e168950. PMID: 37395276, PMCID: PMC10313360, DOI: 10.1172/jci168950.Peer-Reviewed Original ResearchConceptsUrinary CXCL9External validation cohortValidation cohortControl groupAIN diagnosisDiscovery cohortKidney tissueDiagnostic biomarkersAcute interstitial nephritisCXCL9 mRNA expressionAcute kidney injuryBiopsy-confirmed diagnosisAvailable clinical testsNational InstituteKidney injuryTubulointerstitial nephritisInterstitial nephritisKidney biopsyHistological confirmationHistological diagnosisTreatment optionsLymphocyte chemotaxisCXCL9MRNA expression differencesPatientsLongitudinal 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 insultThe ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis
Chernova I, Song W, Steach H, Hafez O, Al Souz J, Chen P, Chandra N, Cantley L, Veselits M, Clark M, Craft J. The ion transporter Na+-K+-ATPase enables pathological B cell survival in the kidney microenvironment of lupus nephritis. Science Advances 2023, 9: eadf8156. PMID: 36724234, PMCID: PMC9891690, DOI: 10.1126/sciadv.adf8156.Peer-Reviewed Original ResearchConceptsB cellsAutoimmune diseasesAmelioration of proteinuriaLupus nephritis biopsiesB cell infiltrationSodium-potassium adenosine triphosphataseB cell survivalPotassium adenosine triphosphataseLupus nephritisCell infiltrationKidney microenvironmentTissue injuryTherapeutic targetPharmacological inhibitionElevated sodium concentrationLupusHostile microenvironmentHigh expressionKidneySodium concentrationGenetic knockoutCell survivalDiseaseCellsAdenosine triphosphatase
2022
Immune-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 5Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy
Baker ML, Yamamoto Y, Perazella MA, Dizman N, Shirali AC, Hafez N, Weinstein J, Simonov M, Testani JM, Kluger HM, Cantley LG, Parikh CR, Wilson FP, Moledina DG. Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy. Journal For ImmunoTherapy Of Cancer 2022, 10: e004421. PMID: 35354588, PMCID: PMC8968986, DOI: 10.1136/jitc-2021-004421.Peer-Reviewed Original ResearchConceptsAcute interstitial nephritisAcute kidney injuryImmune checkpoint inhibitor therapyCheckpoint inhibitor therapyICI therapyKidney injuryInhibitor therapyInterstitial nephritisTime-varying Cox proportional hazards modelsHigher peak serum creatinineSevere acute kidney injuryCancer typesCox proportional hazards modelAssociations of biopsyBaseline laboratory valuesObservational cohort studyPeak serum creatinineFavorable treatment responseProportional hazards modelAKI patientsTherapy initiationCohort studySerum creatinineUnivariable analysisImmune activationCharacterization 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
Cadherin-11, Sparc-related modular calcium binding protein-2, and Pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis
Schmidt I, Colona M, Kestenbaum B, Alexopoulos L, Palsson R, Srivastava A, Liu J, Stillman I, Rennke H, Vaidya V, Wu H, Humphreys B, Waikar S, Knight R, Lecker S, Stillman I, Bogen S, Amodu A, Ilori T, Maikhor S, Schmidt I, Beck L, Henderson J, Onul I, Verma A, McMahon G, Valerius M, Waikar S, Weins A, Colona M, Greka A, Hacohen N, Hoover P, Marshall J, Aulisio M, Chen Y, Janowczyk A, Jayapandian C, Viswanathan V, Bush W, Crawford D, Madabhushi A, Bush L, Cooperman L, Gonzalez-Vicente A, Herlitz L, Jolly S, Nguyen J, O’toole J, Palmer E, Poggio E, Sedor J, Sendrey D, Spates-Harden K, Taliercio J, Bjornstad P, Pyle L, Vinovskis C, Appelbaum P, Balderes O, Barasch J, Bomback A, Canetta P, D’Agati V, Kiryluk K, Kudose S, Mehl K, Shang N, Bansal S, Alexandrov T, Rennke H, El-Achkar T, Barwinska D, Bledso S, Borner K, Bueckle A, Cheng Y, Dagher P, Dunn K, Eadon M, Ferkowicz M, Herr B, Kelly K, Ferreira R, Quardokus E, Record E, Rivera M, Su J, Sutton T, Williams J, Winfree S, Jain Y, Menez S, Parikh C, Rosenberg A, Corona-Villalobos C, Wen Y, Johansen C, Rosas S, Roy N, Sun J, Williams M, Azeloglu E, Hansen J, He C, Iyengar R, Xiong Y, Prasad P, Srivastava A, Madhavan S, Parikh S, Rovin B, Shapiro J, Anderton C, Lukowski J, Pasa-Tolic L, Velickovic D, Oliver G, Ardayfio J, Bebiak J, Brown K, Campbell T, Campbell C, Hayashi L, Jefferson N, Roberts G, Saul J, Shpigel A, Stutzke C, Koewler R, Pinkeney R, Sealfon R, Troyanskaya O, Wong A, Tuttle K, Pollack A, Goltsev Y, Ginley B, Lucarelli N, Lutnick B, Sarder P, Lake B, Zhang K, Boada P, Laszik Z, Nolan G, Anjani K, Sarwal M, Mukatash T, Sigdel T, Alloway R, Burg A, Lee P, Rike A, Shi T, Woodle E, Ascani H, Balis U, Blanc V, Conser N, Eddy S, Frey R, He Y, Hodgin J, Kretzler M, Lienczewski C, Luo J, Mariani L, Menon R, Otto E, Schaub J, Steck B, Elder M, Gilliam M, Hall D, Murugan R, Palevsky P, Randhawa P, Rosengart M, Tublin M, Vita T, Winters J, Kellum J, Alpers C, Berglund A, Berry B, Blank K, Carson J, Daniel S, De Boer I, Dighe A, Dowd F, Grewenow S, Himmelfarb J, Hoofnagle A, Limonte C, McClelland R, Mooney S, Rezaei K, Shankland S, Snyder J, Wang R, Wilcox A, Williams K, Park C, Bansal S, Montellano R, Pamreddy A, Sharma K, Venkatachalam M, Ye H, Zhang G, Basit M, Hedayati S, Kermani A, Lee S, Lu C, Miller R, Moe O, Patel J, Pillai A, Sambandam K, Torrealba J, Toto R, Vazquez M, Wang N, Wen N, Zhang D, Park H, Caprioli R, Patterson N, Sharman K, Spraggins J, Van de Plas R, Basta J, Diettman S, Gaut J, Jain S, Rauchman M, Vijayan A, Cantley L, Kakade V, Moledina D, Shaw M, Ugwuowo U, Wilson F, Arora T. Cadherin-11, Sparc-related modular calcium binding protein-2, and Pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis. Kidney International 2021, 100: 672-683. PMID: 34051265, PMCID: PMC8384690, DOI: 10.1016/j.kint.2021.04.037.Peer-Reviewed Original ResearchConceptsPigment epithelium-derived factorBoston Kidney Biopsy CohortEnd-stage kidney diseaseChronic kidney diseaseModular calcium binding protein-2Seattle Kidney StudyKidney fibrosisKidney diseaseEpithelium-derived factorNon-invasive biomarkersBiopsy cohortTubular atrophyInterstitial fibrosisKidney StudyBinding protein 2Cox proportional hazards regression modelHuman chronic kidney diseaseProportional hazards regression modelsUrine biomarker levelsCohort of patientsHazards regression modelsPromising non-invasive biomarkerIndependent prospective cohortsAssociation of biomarkersNon-invasive assessment
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 persistDevelopment of a 2-dimensional atlas of the human kidney with imaging mass cytometry
Singh N, Avigan ZM, Kliegel JA, Shuch BM, Montgomery RR, Moeckel GW, Cantley LG. Development of a 2-dimensional atlas of the human kidney with imaging mass cytometry. JCI Insight 2019, 4: e129477. PMID: 31217358, PMCID: PMC6629112, DOI: 10.1172/jci.insight.129477.Peer-Reviewed Original ResearchConceptsCell typesIndividual cell typesCritical baseline dataRenal cell typesMass cytometryQuantitative atlasNormal human samplesHuman kidneyRelative abundanceDevelopment of therapiesHuman kidney diseaseKidney diseaseMetal-conjugated antibodiesQuantitative interrogationScarce samplesMachine-learning pipelineDiscovery purposesFuture quantitative analysisNovel abnormalityNormal human kidneySingle tissue sectionHuman samplesRenal biopsyImmune cellsCellsUrine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis
Moledina DG, Wilson FP, Pober JS, Perazella MA, Singh N, Luciano RL, Obeid W, Lin H, Kuperman M, Moeckel GW, Kashgarian M, Cantley LG, Parikh CR. Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis. JCI Insight 2019, 4: e127456. PMID: 31092735, PMCID: PMC6542610, DOI: 10.1172/jci.insight.127456.Peer-Reviewed Original ResearchConceptsAcute interstitial nephritisAcute kidney diseasePrebiopsy diagnosisKidney biopsyKidney diseaseIL-9AIN diagnosisUrine TNFInterstitial nephritisSpecific T cell subsetsAcute tubular injuryDiabetic kidney diseaseIL-9 levelsTNF-α levelsT cell subsetsAddition of biomarkersPlasma cytokinesCytokine levelsTubular injuryHighest quartileMultivariable analysisCell subsetsUrinary TNFBlood eosinophilsGlomerular disease
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 signaling
2013
Met Activation Is Required for Early Cytoprotection after Ischemic Kidney Injury
Mason S, Hader C, Marlier A, Moeckel G, Cantley LG. Met Activation Is Required for Early Cytoprotection after Ischemic Kidney Injury. Journal Of The American Society Of Nephrology 2013, 25: 329-337. PMID: 24136921, PMCID: PMC3904569, DOI: 10.1681/asn.2013050473.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAnimalsApoptosisBcl-Associated Death ProteinGene Knockdown TechniquesKidneyKidney Tubules, ProximalMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphorylationProtein Processing, Post-TranslationalProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesReperfusion InjuryRibosomal Protein S6 Kinases, 70-kDaSignal TransductionConceptsIschemia/reperfusionKidney injuryIschemic injuryProximal tubulesInitial tubular injuryMET receptor expressionProximal tubule responseTubular cell survivalIschemic kidney injuryProximal tubule epithelial cellsRenal proximal tubule epithelial cellsTubular cell proliferationTubular cell apoptosisPI3K/Akt activationProapoptotic factor BadTubule epithelial cellsCell survivalTubule responseSerum creatinineTubular injuryKidney repairLiver abnormalitiesReceptor expressionInjuryMET activationChitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function
Schmidt IM, Hall IE, Kale S, Lee S, He CH, Lee Y, Chupp GL, Moeckel GW, Lee CG, Elias JA, Parikh CR, Cantley LG. Chitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function. Journal Of The American Society Of Nephrology 2013, 24: 309-319. PMID: 23291472, PMCID: PMC3559482, DOI: 10.1681/asn.2012060579.Peer-Reviewed Original ResearchMeSH KeywordsAdipokinesAnimalsApoptosisBiomarkersCells, CulturedChitinase-3-Like Protein 1Delayed Graft FunctionDisease Models, AnimalEpithelial CellsGlycoproteinsHumansKidneyKidney TransplantationLectinsMacrophagesMaleMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesPredictive Value of TestsProto-Oncogene Proteins c-aktReperfusion InjurySignal TransductionTransplantation, HomologousConceptsBRP-39/YKLGraft functionKidney injuryYKL-40Reparative responseDeceased donor kidney transplantationKidney ischemia/reperfusionHours of transplantImmediate graft functionDelayed graft functionTubular cell deathIschemia/reperfusionDegree of injuryAllograft functionCell apoptotic deathKidney hypoperfusionKidney transplantationSystemic hypotensionRenal failureIschemic injuryRenal ischemiaRenal responseUrinary levelsBRP-39Activation of Akt
2011
Distinct Macrophage Phenotypes Contribute to Kidney Injury and Repair
Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi BS, Ruhrberg C, Cantley LG. Distinct Macrophage Phenotypes Contribute to Kidney Injury and Repair. Journal Of The American Society Of Nephrology 2011, 22: 317-326. PMID: 21289217, PMCID: PMC3029904, DOI: 10.1681/asn.2009060615.Peer-Reviewed Original ResearchConceptsTubular cell proliferationProinflammatory macrophagesM2 phenotypeKidney injuryKidney repairInterstitial inflammatory cell infiltrateIschemia/reperfusion injuryRenal tubular cell proliferationTubular cell necrosisInflammatory cell infiltrateMacrophage-depleted miceDepletion of macrophagesIschemia/reperfusionBone marrow-derived macrophagesCell proliferationRenal tubular cellsMarrow-derived macrophagesAppearance of macrophagesLater time pointsKidney reperfusionTubule injuryCell infiltrateReperfusion injuryKidney damageMacrophage depletion
2001
Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud
Karihaloo A, Karumanchi S, Barasch J, Jha V, Nickel C, Yang J, Grisaru S, Bush K, Nigam S, Rosenblum N, Sukhatme V, Cantley L. Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 12509-12514. PMID: 11606725, PMCID: PMC60084, DOI: 10.1073/pnas.221205198.Peer-Reviewed Original Research
2000
Differential MAPK Pathways Utilized for HGF- and EGF-dependent Renal Epithelial Morphogenesis*
Karihaloo A, O'Rourke D, Nickel C, Spokes K, Cantley L. Differential MAPK Pathways Utilized for HGF- and EGF-dependent Renal Epithelial Morphogenesis*. Journal Of Biological Chemistry 2000, 276: 9166-9173. PMID: 11118451, DOI: 10.1074/jbc.m009963200.Peer-Reviewed Original ResearchConceptsHepatocyte growth factorP42/44 mitogen-activated protein kinase (MAPK) pathwayEGF-induced cell motilityProtein kinase kinase inhibitor PD98059Mitogen-activated protein kinase kinase inhibitor PD98059Mitogen-activated protein kinase pathwayEGF-dependent migrationProcess formationEGF-stimulated cellsRenal epithelial morphogenesisIndependent signaling pathwaysKinase inhibitor PD98059ERK1/ERK2Protein kinase pathwayEpidermal growth factor receptor ligandsCultured renal epithelial cellsLigand hepatocyte growth factorGrowth factor receptor ligandsCell morphogenesisEpithelial morphogenesisRenal epithelial cellsMKK1 inhibitorCell motilityKinase pathwayInhibitor PD98059Hepatocyte growth factor induces MAPK-dependent formin IV translocation in renal epithelial cells.
O'Rourke DA, Liu ZX, Sellin L, Spokes K, Zeller R, Cantley L. Hepatocyte growth factor induces MAPK-dependent formin IV translocation in renal epithelial cells. Journal Of The American Society Of Nephrology 2000, 11: 2212-2221. PMID: 11095644, DOI: 10.1681/asn.v11122212.Peer-Reviewed Original ResearchConceptsFormin isoformsHepatocyte growth factorRenal epithelial cellsEpithelial tubule formationProtein kinase-dependent mannerUreteric bud outgrowthExtracellular signal-regulated kinaseQuiescent epithelial cellsEpithelial cellsFamily of proteinsProtein kinase inhibitor U0126Mitogen-activated protein kinase-dependent mannerKinase-dependent mannerMitogen-activated protein kinase inhibitor U0126Kinase inhibitor U0126Cell-matrix interactionsCell-cell interactionsGrowth factorSignal-regulated kinaseTubule formationSoluble cell lysateRapid relocalizationPhosphorylation substratesActin cytoskeletonCellular relocalizationReactive Oxygen Species Expose Cryptic Epitopes Associated with Autoimmune Goodpasture Syndrome*
Kalluri R, Cantley L, Kerjaschki D, Neilson E. Reactive Oxygen Species Expose Cryptic Epitopes Associated with Autoimmune Goodpasture Syndrome*. Journal Of Biological Chemistry 2000, 275: 20027-20032. PMID: 10748075, DOI: 10.1074/jbc.m904549199.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Glomerular Basement Membrane DiseaseAutoantibodiesBasement MembraneCollagenDose-Response Relationship, DrugEnzyme-Linked Immunosorbent AssayEpitopesFluorescent Antibody TechniqueHumansHydrogen PeroxideKidneyMiceMice, Inbred BALB CProtein Structure, TertiaryRatsReactive Oxygen SpeciesTime FactorsConceptsGoodpasture's syndromeReactive oxygen speciesGoodpasture epitopeType IV collagenRenal transplant recipientsIV collagenEffects of ROSTime-dependent fashionTransplant recipientsNeoantigen formationAutoantibody productionImmune activationAutoimmune diseasesHydrogen peroxide administrationAge-dependent deteriorationT cellsNon-collagenous globular domainsImmune systemEpitope diversityCryptic epitopesSyndromeAlport syndromeHeterologous antibodiesGoodpasture antibodyEpitopes