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

被引:19
作者
Gonzalez-Herrera, IG
Prado-Lourenco, L
Teshima-Kondo, S
Kondo, K
Cabon, F
Arnal, JF
Bayard, F
Prats, AC [1 ]
机构
[1] CHU Rangueil, Inst Louis Bugnard, IFR31, INSERM,U589, Batiment L3,Ave Jean Poulhes,BP 84225, F-31432 Toulouse 4, France
[2] MilleGen, Prologue Biotech, F-31319 Labege, France
[3] Univ Tokushima, Sch Med, Dept Nutr, Tokushima 7708503, Japan
[4] CNRS, UPR 9079, Inst Andre Lwoff, Lab Oncogenese Differenciat & Transduct Signal, F-94800 Villejuif, France
关键词
diabetes; fibroblast growth factor 2 (FGF-2); heterogeneous nuclear ribonucleoprotein AI (hnRNP AI); internal ribosome entry site (IRES); p53; transgenic mouse; translation control;
D O I
10.1042/BST0340017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 of hnRNP Al (heterogeneous nuclear ribonucleoprotein Al), recently identified as inhibitory or activatory ITAFs respectively for FGF-2 IRES.
引用
收藏
页码:17 / 21
页数:5
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