Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/74888
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dc.contributor.authorRecio Cruz, Carlota Pilaren_US
dc.contributor.authorLazaro, Iolandaen_US
dc.contributor.authorOguiza, Ainhoaen_US
dc.contributor.authorLópez-Sanz, Lauraen_US
dc.contributor.authorBernal, Susanaen_US
dc.contributor.authorBlanco, Juliaen_US
dc.contributor.authorEgido, Jesusen_US
dc.contributor.authorGómez-Guerrero, Carmenen_US
dc.date.accessioned2020-10-20T09:55:49Z-
dc.date.available2020-10-20T09:55:49Z-
dc.date.issued2017en_US
dc.identifier.issn1046-6673en_US
dc.identifier.urihttp://hdl.handle.net/10553/74888-
dc.description.abstractDiabetes is the main cause of CKD and ESRD worldwide. Chronic activation of Janus kinase and signal transducer and activator of transcription (STAT) signaling contributes to diabetic nephropathy by inducing genes involved in leukocyte infiltration, cell proliferation, and extracellular matrix accumulation. This study examined whether a cell-permeable peptide mimicking the kinase-inhibitory region of suppressor of cytokine signaling-1 (SOCS1) regulatory protein protects against nephropathy by suppressing STAT-mediated cell responses to diabetic conditions. In a mouse model combining hyperglycemia and hypercholesterolemia (streptozotocin diabetic, apoE-deficient mice), renal STAT activation status correlated with the severity of nephropathy. Notably, compared with administration of vehicle or mutant inactive peptide, administration of the SOCS1 peptidomimetic at either early or advanced stages of diabetes ameliorated STAT activity and resulted in reduced serum creatinine level, albuminuria, and renal histologic changes (mesangial expansion, tubular injury, and fibrosis) over time. Mice treated with the SOCS1 peptidomimetic also exhibited reduced kidney leukocyte recruitment (T lymphocytes and classic M1 proinflammatory macrophages) and decreased expression levels of proinflammatory and profibrotic markers that were independent of glycemic and lipid changes. In vitro, internalized peptide suppressed STAT activation and target gene expression induced by inflammatory and hyperglycemic conditions, reduced migration and proliferation in mesangial and tubuloepithelial cells, and altered the expression of cytokine-induced macrophage polarization markers. In conclusion, our study identifies SOCS1 mimicking as a feasible therapeutic strategy to halt the onset and progression of renal inflammation and fibrosis in diabetic kidney disease.en_US
dc.languageengen_US
dc.relation.ispartofJournal of the American Society of Nephrology : JASNen_US
dc.sourceJournal of the American Society of Nephrology : JASN [ISSN 1046-6673], v. 28 (2), p. 575-585en_US
dc.subject320502 Endocrinologíaen_US
dc.subject.otherChronic inflammationen_US
dc.subject.otherDiabetic nephropathyen_US
dc.subject.otherFibrosisen_US
dc.subject.otherMacrophagesen_US
dc.subject.otherTranscription factorsen_US
dc.subject.otherApolipoprotein Een_US
dc.titleSuppressor of Cytokine Signaling-1 Peptidomimetic Limits Progression of Diabetic Nephropathyen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.typeArticleen_US
dc.identifier.doi10.1681/ASN.2016020237en_US
dc.description.lastpage585en_US
dc.identifier.issue2-
dc.description.firstpage575en_US
dc.relation.volume28en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.utils.revisionen_US
dc.identifier.ulpgcNoen_US
dc.contributor.buulpgcBU-MEDen_US
dc.description.sjr4,819
dc.description.jcr8,655
dc.description.sjrqQ1
dc.description.jcrqQ1
dc.description.scieSCIE
item.grantfulltextopen-
item.fulltextCon texto completo-
crisitem.author.deptGIR IUIBS: Farmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.orcid0000-0002-8832-2826-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameRecio Cruz, Carlota Pilar-
Colección:Artículos
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