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

Shigetada Teshima-Kondo (1) , Kazumi Kondo (1) , Leonel Prado-Lourenco (1) , Irma G. Gonzalez-Herrera (1) , Kazuhito Rokutan (1) , Francis Bayard (1) , Jean-François Arnal (1) , Anne-Catherine Prats (1)

1 Hormones, facteurs de croissance et physiopathologie vasculaire

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.

Mots clés: FGF-2 • IRES • STZ • SMC

Domaines: Médecine humaine et pathologie

Shigetada Teshima-Kondo, Kazumi Kondo, Leonel Prado-Lourenco, Irma G. 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, 2004, 18 (13), pp.1583-5. ⟨10.1096/fj.03-1118fje⟩. ⟨hal-00307743⟩