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Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells
We have shown the full prevention of mesangial expansion in insulin-deficient diabetic rats by treatment with clinically-relevant dosages of glibenclamide (Glib). Studies in mesangial cells (MCs) also demonstrated reduction in the high glucose (HG)-induced accumulation of collagens, proposing that t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447387/ https://www.ncbi.nlm.nih.gov/pubmed/23008698 http://dx.doi.org/10.1155/2012/183535 |
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author | Zhu, Liping Cortes, Pedro Hassett, Clare Taube, David W. Yee, Jerry |
author_facet | Zhu, Liping Cortes, Pedro Hassett, Clare Taube, David W. Yee, Jerry |
author_sort | Zhu, Liping |
collection | PubMed |
description | We have shown the full prevention of mesangial expansion in insulin-deficient diabetic rats by treatment with clinically-relevant dosages of glibenclamide (Glib). Studies in mesangial cells (MCs) also demonstrated reduction in the high glucose (HG)-induced accumulation of collagens, proposing that this was due to increased catabolism. In the present study, we investigated the signaling pathways that may be implicated in Glib action. Rat primary MCs were exposed to HG for 8 weeks with or without Glib in therapeutic (0.01 μM) or supratherapeutic (1.0 μM) concentrations. We found that HG increased collagen IV protein accumulation and PAI-1 mRNA and protein expression, in association with decreased cAMP generating capacity and decreased PKA activity. Low Glib increased collagen IV mRNA but fully prevented collagen IV protein accumulation and PAI-1 overexpression while enhancing cAMP formation and PKA activity. MMP2 mRNA, protein expression and gelatinolytic activity were also enhanced. High Glib was, overall, ineffective. In conclusion, low dosage/concentration Glib prevents HG-induced collagen accumulation in MC by enhancing collagen catabolism in a cAMP-PKA-mediated PAI-1 inhibition. |
format | Online Article Text |
id | pubmed-3447387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-34473872012-09-24 Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells Zhu, Liping Cortes, Pedro Hassett, Clare Taube, David W. Yee, Jerry Exp Diabetes Res Research Article We have shown the full prevention of mesangial expansion in insulin-deficient diabetic rats by treatment with clinically-relevant dosages of glibenclamide (Glib). Studies in mesangial cells (MCs) also demonstrated reduction in the high glucose (HG)-induced accumulation of collagens, proposing that this was due to increased catabolism. In the present study, we investigated the signaling pathways that may be implicated in Glib action. Rat primary MCs were exposed to HG for 8 weeks with or without Glib in therapeutic (0.01 μM) or supratherapeutic (1.0 μM) concentrations. We found that HG increased collagen IV protein accumulation and PAI-1 mRNA and protein expression, in association with decreased cAMP generating capacity and decreased PKA activity. Low Glib increased collagen IV mRNA but fully prevented collagen IV protein accumulation and PAI-1 overexpression while enhancing cAMP formation and PKA activity. MMP2 mRNA, protein expression and gelatinolytic activity were also enhanced. High Glib was, overall, ineffective. In conclusion, low dosage/concentration Glib prevents HG-induced collagen accumulation in MC by enhancing collagen catabolism in a cAMP-PKA-mediated PAI-1 inhibition. Hindawi Publishing Corporation 2012 2012-09-12 /pmc/articles/PMC3447387/ /pubmed/23008698 http://dx.doi.org/10.1155/2012/183535 Text en Copyright © 2012 Liping Zhu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhu, Liping Cortes, Pedro Hassett, Clare Taube, David W. Yee, Jerry Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells |
title | Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells |
title_full | Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells |
title_fullStr | Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells |
title_full_unstemmed | Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells |
title_short | Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells |
title_sort | glibenclamide induces collagen iv catabolism in high glucose-stimulated mesangial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447387/ https://www.ncbi.nlm.nih.gov/pubmed/23008698 http://dx.doi.org/10.1155/2012/183535 |
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