Redefining the role of ADAM17 in renal proximal tubular cells and its implications in an obese mouse model of pre-diabetes

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• dc.contributor.author Palau González, Vanesa
• dc.contributor.author Villanueva, Sofia
• dc.contributor.author Jarrín, Josué
• dc.contributor.author Benito, David
• dc.contributor.author Márquez, Eva
• dc.contributor.author Rodríguez, Eva
• dc.contributor.author Soler, María José
• dc.contributor.author Oliveras, Anna
• dc.contributor.author Gimeno Beltran, Javier
• dc.contributor.author Sans Atxer, Laia
• dc.contributor.author Crespo Barrio, Marta
• dc.contributor.author Pascual Santos, Julio
• dc.contributor.author Barrios Barrera, Clara
• dc.contributor.author Riera Oliva, Marta
• dc.date.accessioned 2022-09-05T06:38:50Z
• dc.date.available 2022-09-05T06:38:50Z
• dc.date.issued 2021
• dc.description.abstract Acute and chronic kidney lesions induce an increase in A Disintegrin And Metalloproteinase domain 17 (ADAM17) that cleaves several transmembrane proteins related to inflammatory and fibrotic pathways. Our group has demonstrated that renal ADAM17 is upregulated in diabetic mice and its inhibition decreases renal inflammation and fibrosis. The purpose of the present study was to analyze how Adam17 deletion in proximal tubules affects different renal structures in an obese mice model. Tubular Adam17 knockout male mice and their controls were fed a high-fat diet (HFD) for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, and pro-inflammatory and pro-fibrotic markers were evaluated. Results showed that wild-type mice fed an HFD became obese with glucose intolerance and renal histological alterations mimicking a pre-diabetic condition; consequently, greater glomerular size and mesangial expansion were observed. Adam17 tubular deletion improved glucose tolerance and protected animals against glomerular injury and prevented podocyte loss in HFD mice. In addition, HFD mice showed more glomerular macrophages and collagen accumulation, which was prevented by Adam17 deletion. Galectin-3 expression increased in the proximal tubules and glomeruli of HFD mice and ameliorated with Adam17 deletion. In conclusion, Adam17 in proximal tubules influences glucose tolerance and participates in the kidney injury in an obese pre-diabetic murine model. The role of ADAM17 in the tubule impacts on glomerular inflammation and fibrosis.
• dc.format.mimetype application/pdf
• dc.identifier.citation Palau V, Villanueva S, Jarrín J, Benito D, Márquez E, Rodríguez E, et al. Redefining the role of ADAM17 in renal proximal tubular cells and its implications in an obese mouse model of pre-diabetes. Int J Mol Sci. 2021 Dec 3; 22(23): 13093. DOI: 10.3390/ijms222313093
• dc.identifier.doi http://dx.doi.org/10.3390/ijms222313093
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/53991
• dc.language.iso eng
• dc.publisher MDPI
• dc.rights Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword ADAM17
• dc.subject.keyword Obesity
• dc.subject.keyword Pre-diabetes
• dc.subject.keyword Renal proximal tubular cells
• dc.title Redefining the role of ADAM17 in renal proximal tubular cells and its implications in an obese mouse model of pre-diabetes
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion