Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells
Joint Authors
Hassett, Clare
Yee, Jerry
Taube, David W.
Cortes, Pedro
Zhu, Liping
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2011), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-09-12
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Zhu, Liping& Cortes, Pedro& Hassett, Clare& Taube, David W.& Yee, Jerry. 2012. Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells. Journal of Diabetes Research،Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-993929
Modern Language Association (MLA)
Zhu, Liping…[et al.]. Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells. Journal of Diabetes Research Vol. 2012, no. 2012 (2011), pp.1-9.
https://search.emarefa.net/detail/BIM-993929
American Medical Association (AMA)
Zhu, Liping& Cortes, Pedro& Hassett, Clare& Taube, David W.& Yee, Jerry. Glibenclamide Induces Collagen IV Catabolism in High Glucose-Stimulated Mesangial Cells. Journal of Diabetes Research. 2012. Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-993929
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-993929