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Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes

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 dec...

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Autores principales: Palau, Vanesa, Villanueva, Sofia, Jarrín, Josué, Benito, David, Márquez, Eva, Rodríguez, Eva, Soler, María José, Oliveras, Anna, Gimeno, Javier, Sans, Laia, Crespo, Marta, Pascual, Julio, Barrios, Clara, Riera, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657896/
https://www.ncbi.nlm.nih.gov/pubmed/34884897
http://dx.doi.org/10.3390/ijms222313093
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author Palau, Vanesa
Villanueva, Sofia
Jarrín, Josué
Benito, David
Márquez, Eva
Rodríguez, Eva
Soler, María José
Oliveras, Anna
Gimeno, Javier
Sans, Laia
Crespo, Marta
Pascual, Julio
Barrios, Clara
Riera, Marta
author_facet Palau, Vanesa
Villanueva, Sofia
Jarrín, Josué
Benito, David
Márquez, Eva
Rodríguez, Eva
Soler, María José
Oliveras, Anna
Gimeno, Javier
Sans, Laia
Crespo, Marta
Pascual, Julio
Barrios, Clara
Riera, Marta
author_sort Palau, Vanesa
collection PubMed
description 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.
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spelling pubmed-86578962021-12-10 Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes Palau, Vanesa Villanueva, Sofia Jarrín, Josué Benito, David Márquez, Eva Rodríguez, Eva Soler, María José Oliveras, Anna Gimeno, Javier Sans, Laia Crespo, Marta Pascual, Julio Barrios, Clara Riera, Marta Int J Mol Sci Article 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. MDPI 2021-12-03 /pmc/articles/PMC8657896/ /pubmed/34884897 http://dx.doi.org/10.3390/ijms222313093 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Palau, Vanesa
Villanueva, Sofia
Jarrín, Josué
Benito, David
Márquez, Eva
Rodríguez, Eva
Soler, María José
Oliveras, Anna
Gimeno, Javier
Sans, Laia
Crespo, Marta
Pascual, Julio
Barrios, Clara
Riera, Marta
Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes
title Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes
title_full Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes
title_fullStr Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes
title_full_unstemmed Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes
title_short Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes
title_sort redefining the role of adam17 in renal proximal tubular cells and its implications in an obese mouse model of pre-diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657896/
https://www.ncbi.nlm.nih.gov/pubmed/34884897
http://dx.doi.org/10.3390/ijms222313093
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