Insulin and insulin-like growth factor-I induce vascular endothelial growth factor mRNA expression via different signaling pathways.
J Biol Chem
; 275(28): 21695-702, 2000 Jul 14.
Article
en En
| MEDLINE
| ID: mdl-10777488
ABSTRACT
In this study we have investigated the molecular mechanisms of insulin and insulin-like growth factor-I (IGF-I) action on vascular endothelial growth factor (VEGF) gene expression. Treatment with insulin or IGF-I for 4 h increased the abundance of VEGF mRNA in NIH3T3 fibroblasts expressing either the human insulin receptor (NIH-IR) or the human IGF-I receptor (NIH-IGFR) by 6- and 8-fold, respectively. The same elevated levels of mRNA were maintained after 24 h of stimulation with insulin, whereas IGF-I treatment further increased VEGF mRNA expression to 12-fold after 24 h. Pre-incubation with the phosphatidylinositol 3-kinase inhibitor wortmannin abolished the effect of insulin on VEGF mRNA expression in NIH-IR cells but did not modify the IGF-I-induced VEGF mRNA expression in NIH-IGFR cells. Blocking mitogen-activated protein kinase activation with the MEK inhibitor PD98059 abolished the effect of IGF-I on VEGF mRNA expression in NIH-IGFR cells but had no effect on insulin-induced VEGF mRNA expression in NIH-IR cells. Expression of a constitutively active PKB in NIH-IR cells induced the expression of VEGF mRNA, which was not further modified by insulin treatment. We conclude that VEGF induction by insulin and IGF-I occurs via different signaling pathways, the former involving phosphatidylinositol 3-kinase/protein kinase B and the latter involving MEK/mitogen-activated protein kinase.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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Factor I del Crecimiento Similar a la Insulina
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Receptor de Insulina
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Transducción de Señal
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Regulación de la Expresión Génica
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Factores de Crecimiento Endotelial
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Linfocinas
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Receptor IGF Tipo 1
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Proteínas Serina-Treonina Quinasas
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Insulina
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2000
Tipo del documento:
Article