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Glibenclamide induces collagen IV catabolism in high glucose-stimulated mesangial cells.

Authors: Zhu, L  Cortes, P  Hassett, C  Taube, DW  Yee, J 
Citation: Zhu L, etal., Exp Diabetes Res. 2012;2012:183535. Epub 2012 Sep 12.
Pubmed: (View Article at PubMed) PMID:23008698
DOI: Full-text: DOI:10.1155/2012/183535

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 muM) or supratherapeutic (1.0 muM) 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.


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CRRD Object Information
CRRD ID: 8547888
Created: 2014-02-27
Species: All species
Last Modified: 2014-02-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.