Liu, KuiLi, Quan-ZhenDelgado-Vega, Angelica MAbelson, Anna-KarinSánchez, ElenaKelly, Jennifer ALi, LiLiu, YangZhou, JinchunYan, MeiYe, QiuLiu, ShenxiXie, ChunZhou, Xin JChung, Sharon APons-Estel, BernardoWitte, TorstenRamón, Enrique deBae, Sang-CheolBarizzone, NadiaSebastiani, Gian DomenicoMerrill, Joan TGregersen, Peter KGilkeson, Gary GKimberly, Robert PVyse, Timothy JKim, IlD'Alfonso, SandraMartin, JavierHarley, John BCriswell, Lindsey AWakeland, Edward KAlarcón-Riquelme, Marta EMohan, ChandraDanieli, Maria GiovannaGaleazzi, MauroQuerini, Patrizia RovereMigliaresi, SergioScherbarth, Hugo RLopez, Jorge AMotta, Estela LGamron, SusanaDrenkard, CristinaMenso, EmiliaAllievi, AlbertoTate, Guillermo APresas, José LPalatnik, Simon AAbdala, MarceloBearzotti, MarielaAlvarellos, AlejandroCaeiro, FranciscoBertoli, AnaPaira, SergioRoverano, SusanaGraf, Cesar EBertero, EstelaCaprarulo, CesarBuchanan, GriseldaGuillerón, CarolinaGrimaudo, SebastianManni, JorgeCatoggio, Luis JSoriano, Enrique RSantos, Carlos DPrigione, CristinaRamos, Fernando ANavarro, Sandra MBerbotto, Guillermo AJorfen, MarisaRomero, Elisa JGarcia, Mercedes AMarcos, Juan CMarcos, Ana IPerandones, Carlos EEimon, AliciaBattagliotti, Cristina GArmadi-Simab, KGross, Wolfgang LGromnica-Ihle, ErikaPeter, Hans-HartmutManger, KarinSchnarr, SebastianZeidler, HenningSchmidt, Reinhold EOrtego, NorbertoCallejas, José LJiménez-Alonso, JuanSabio, MarioSánchez-Román, JulioGarcia-Hernandez, Francisco JCamps, MayteLópez-Nevot, Miguel AngelGonzález-Escribano, Maria FHarley, John HKimberly, RobertCriswell, LindseyLangefeld, CarlTsao, BettyJacob, Chaim2013-03-122013-03-122009-04Liu K, Li QZ, Delgado-Vega AM, Abelson AK, Sánchez E, Kelly JA, et al. Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans. J. Clin. Invest.. 2009 Apr; 119(4):911-230021-9738http://hdl.handle.net/10668/816Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.enAnimalesSecuencia de BasesDNAModelos animales de enfermedadFemeninoPerfiles de expresión génicaMembrana basal glomerularHumanosCalicreínasLupus eritematoso sistémicoNefritis lúpicaRatonesRatones consanguíneos BALB CRatones consanguíneos DBADatos de Secuencia MolecularAnálisis de secuencia de alineamiento de oligonucleótidosPolimorfismo genéticoHomología de Secuencia de Ácido NucleicoEspecificidad de la EspecieMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Base SequenceMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNAMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Animal::Disease Models, AnimalMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression ProfilingMedical Subject Headings::Anatomy::Cells::Cellular Structures::Extracellular Space::Extracellular Matrix::Glomerular Basement MembraneMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Biological Factors::Blood Coagulation Factors::KallikreinsMedical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, SystemicMedical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Lupus Erythematosus, Systemic::Lupus NephritisMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred BALB CMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred DBAMedical Subject Headings::Information Science::Information Science::Information Services::Documentation::Molecular Sequence DataMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Molecular Probe Techniques::Oligonucleotide Array Sequence AnalysisMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, GeneticMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Sequence Homology::Sequence Homology, Nucleic AcidMedical Subject Headings::Phenomena and Processes::Biological Phenomena::Species SpecificityMedical Subject Headings::Organisms::Eukaryota::Animalsresearch article19307730open access10.1172/JCI367281558-8238