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Hyperglycemia upregulates translation of the fibroblast growth factor 2 mRNA in mouse aorta via internal ribosome entry site.

Abstract : Fibroblast growth factor 2 (FGF-2) is normally synthesized at low levels but is elevated in various pathophysiological conditions including diabetes-associated vascular diseases. FGF-2 expression is regulated translationally through an internal ribosome entry site (IRES) located in its mRNA, which allows a nonclassical cap-independent translation. We addressed the pathophysiological regulation of the IRES in vivo by using a streptozotocin-induced hyperglycemic model known to suppress markedly overall translation. Evaluation of FGF-2 IRES-dependent translation was performed with transgenic mice expressing dual luciferase bicistronic mRNA containing the FGF-2 IRES. FGF-2 IRES-dependent reporter activity increased 240% of control in the diabetic aorta although the reporter mRNA levels significantly decreased. Expression of endogenous FGF-2 protein in the aorta closely correlated with the IRES activity but not with FGF-2 mRNA levels. Moreover, the biosynthesis of endogenous FGF-2 protein was stimulated in an IRES-dependent manner by high glucose that significantly suppressed global protein synthesis in aortic smooth muscle cells from the transgenic mice. These results suggest that IRES-dependent translational regulation could play a pathological role in FGF-2 expression in vivo, especially in the cardiovascular consequences of diabetes.
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https://www.hal.inserm.fr/inserm-00162046
Contributor : Nicole Blanquart <>
Submitted on : Thursday, July 12, 2007 - 11:33:29 AM
Last modification on : Friday, January 10, 2020 - 9:09:03 PM
Long-term archiving on: : Friday, November 25, 2016 - 4:59:17 PM

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Shigetada Teshima-Kondo, Kazumi Kondo, Leonel Prado-Lourenco, Irma Gabriela Gonzalez-Herrera, Kazuhito Rokutan, et al.. Hyperglycemia upregulates translation of the fibroblast growth factor 2 mRNA in mouse aorta via internal ribosome entry site.. FASEB Journal, Federation of American Society of Experimental Biology, 2004, 18 (13), pp.1583-5. ⟨10.1096/fj.03-1118fje⟩. ⟨inserm-00162046⟩

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