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Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats

Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and d...

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Autores principales: Molina-Jijón, Eduardo, Rodríguez-Muñoz, Rafael, González-Ramírez, Ricardo, Namorado-Tónix, Carmen, Pedraza-Chaverri, José, Reyes, Jose L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426686/
https://www.ncbi.nlm.nih.gov/pubmed/28493961
http://dx.doi.org/10.1371/journal.pone.0177362
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author Molina-Jijón, Eduardo
Rodríguez-Muñoz, Rafael
González-Ramírez, Ricardo
Namorado-Tónix, Carmen
Pedraza-Chaverri, José
Reyes, Jose L.
author_facet Molina-Jijón, Eduardo
Rodríguez-Muñoz, Rafael
González-Ramírez, Ricardo
Namorado-Tónix, Carmen
Pedraza-Chaverri, José
Reyes, Jose L.
author_sort Molina-Jijón, Eduardo
collection PubMed
description Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ), and SPL was administrated daily by gavage, from days 3–21. Twenty-one days after STZ injection the rats were sacrificed. In diabetic rats, the serum ALD levels were increased, and SPL-treatment did not have effect on these levels or in hyperglycemia, however, proteinuria decreased in SPL-treated diabetic rats. Glomerular damage, evaluated by nephrin and Wilm’s tumor 1 (WT1) protein expressions, and proximal tubular damage, evaluated by kidney injury molecule 1 (Kim-1) and heat shock protein 72 kDa (Hsp72) expressions, were ameliorated by SPL. Also, SPL prevented decrement in claudin-5 in glomeruli, and claudin-2 and occludin in proximal tubules by decreasing oxidative stress, evaluated by superoxide anion (O(2)(●―)) production, and oxidative stress markers. In distal tubules, SPL ameliorated increase in mRNA, protein expression, and phosphorylation in threonine residues of claudin-4 and -8, through a serum and glucocorticoid-induced kinase 1 (SGK1), and with-no-lysine kinase 4 (WNK4) signaling pathway. In conclusion, this is the first study that demonstrates that ALD modulates the expression of renal TJ proteins in diabetes, and that the blockade of its actions with SPL, may be a promising therapeutic strategy to prevent alterations of TJ proteins in diabetic nephropathy.
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spelling pubmed-54266862017-05-25 Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats Molina-Jijón, Eduardo Rodríguez-Muñoz, Rafael González-Ramírez, Ricardo Namorado-Tónix, Carmen Pedraza-Chaverri, José Reyes, Jose L. PLoS One Research Article Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ), and SPL was administrated daily by gavage, from days 3–21. Twenty-one days after STZ injection the rats were sacrificed. In diabetic rats, the serum ALD levels were increased, and SPL-treatment did not have effect on these levels or in hyperglycemia, however, proteinuria decreased in SPL-treated diabetic rats. Glomerular damage, evaluated by nephrin and Wilm’s tumor 1 (WT1) protein expressions, and proximal tubular damage, evaluated by kidney injury molecule 1 (Kim-1) and heat shock protein 72 kDa (Hsp72) expressions, were ameliorated by SPL. Also, SPL prevented decrement in claudin-5 in glomeruli, and claudin-2 and occludin in proximal tubules by decreasing oxidative stress, evaluated by superoxide anion (O(2)(●―)) production, and oxidative stress markers. In distal tubules, SPL ameliorated increase in mRNA, protein expression, and phosphorylation in threonine residues of claudin-4 and -8, through a serum and glucocorticoid-induced kinase 1 (SGK1), and with-no-lysine kinase 4 (WNK4) signaling pathway. In conclusion, this is the first study that demonstrates that ALD modulates the expression of renal TJ proteins in diabetes, and that the blockade of its actions with SPL, may be a promising therapeutic strategy to prevent alterations of TJ proteins in diabetic nephropathy. Public Library of Science 2017-05-11 /pmc/articles/PMC5426686/ /pubmed/28493961 http://dx.doi.org/10.1371/journal.pone.0177362 Text en © 2017 Molina-Jijón et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Molina-Jijón, Eduardo
Rodríguez-Muñoz, Rafael
González-Ramírez, Ricardo
Namorado-Tónix, Carmen
Pedraza-Chaverri, José
Reyes, Jose L.
Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats
title Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats
title_full Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats
title_fullStr Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats
title_full_unstemmed Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats
title_short Aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats
title_sort aldosterone signaling regulates the over-expression of claudin-4 and -8 at the distal nephron from type 1 diabetic rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426686/
https://www.ncbi.nlm.nih.gov/pubmed/28493961
http://dx.doi.org/10.1371/journal.pone.0177362
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