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IRES-dependent regulation of FGF-2 mRNA translation in pathophysiological conditions in the mouse.

Abstract : The mRNA coding for FGF-2 (fibroblast growth factor 2), a major angiogenic factor, is translated by an IRES (internal ribosome entry site)-dependent mechanism. We have studied the role of the IRES in the regulation of FGF-2 expression in vivo, under pathophysiological conditions, by creating transgenic mice lines expressing bioluminescent bicistronic transgenes. Analysis of FGF-2 IRES activity indicates strong tissue specificity in adult brain and testis, suggesting a role of the IRES in the activation of FGF-2 expression in testis maturation and brain function. We have explored translational control of FGF-2 mRNA under diabetic hyperglycaemic conditions, as FGF-2 is implied in diabetes-related vascular complications. FGF-2 IRES is specifically activated in the aorta wall in streptozotocin-induced diabetic mice, in correlation with increased expression of endogenous FGF-2. Thus, under hyperglycaemic conditions, where cap-dependent translation is blocked, IRES activation participates in FGF-2 overexpression, which is one of the keys of diabetes-linked atherosclerosis aggravation. IRES activation under such pathophysiological conditions may involve ITAFs (IRES trans-acting factors), such as p53 or hnRNP AI (heterogeneous nuclear ribonucleoprotein AI), recently identified as inhibitory or activatory ITAFs respectively for FGF-2 IRES.
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https://www.hal.inserm.fr/inserm-00091601
Contributor : Annick Harel-Bellan <>
Submitted on : Wednesday, September 6, 2006 - 5:04:49 PM
Last modification on : Friday, January 10, 2020 - 9:09:03 PM
Long-term archiving on: : Tuesday, April 6, 2010 - 12:48:10 AM

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Irma Gonzalez-Herrera, Leonel Prado-Lourenco, Shigetada Teshima-Kondo, Kazumi Kondo, Florence Cabon, et al.. IRES-dependent regulation of FGF-2 mRNA translation in pathophysiological conditions in the mouse.. Biochem Soc Trans, 2006, 34, pp.17-21. ⟨10.1042/BST20060017⟩. ⟨inserm-00091601⟩

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