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Hyperglycemia upregulates translation of the fibroblast growth factor 2 mRNA in mouse aorta via internal ribosome entry site
Author(s) -
TeshimaKondo Shigetada,
Kondo Kazumi,
PradoLourenco Leonel,
Gabriela GonzalezHerrera Irma,
Rokutan Kazuhito,
Bayard Francis,
Arnal JeanFrançois,
Prats AnneCatherine
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-1118fje
Subject(s) - internal ribosome entry site , translation (biology) , messenger rna , protein biosynthesis , fibroblast growth factor , microbiology and biotechnology , in vivo , biology , translational regulation , transgene , reporter gene , chemistry , gene expression , gene , receptor , biochemistry , genetics
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.