Insulin and insulin-like growth factor-I induce vascular endothelial growth factor mRNA expression via different signaling pathways

Citation
C. Miele et al., Insulin and insulin-like growth factor-I induce vascular endothelial growth factor mRNA expression via different signaling pathways, J BIOL CHEM, 275(28), 2000, pp. 21695-21702
Citations number
67
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
28
Year of publication
2000
Pages
21695 - 21702
Database
ISI
SICI code
0021-9258(20000714)275:28<21695:IAIGFI>2.0.ZU;2-Z
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 incr eased the abundance of VEGF mRNA in NIH3T3 fibroblasts expressing either th e 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 maintai ned 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-acti vated protein kinase activation with the MEK inhibitor PD98059 abolished th e effect of IGF-I on VEGF mRNA expression in NIH-IGFR cells but had no effe ct 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 m RNA, 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 t he latter involving MEK/mitogen-activated protein kinase.