AIMTo investigate the cellular signal transduction pathway of vascular smooth muscle cell (VSMC) proliferation stimulated by insulin-like growth factor-1 (IGF-1).

METHODSRabbit aortic VSMCs was cultured in 3 groups. Cell proliferating ability was determined by measuring cell number and mitochondrial dehydrogenase (MD) activity (MTT assay). Wortmannin (WT), the specific inhibitor of phosphatidylinositol 3-kinase (PI3K), was used to evaluate indirectly the possible involvement of PI3K. Western blotting was used to detect the protein expression of phosphatase PTEN. Diphosphate action of PTEN on its specific substrate diC16PIP3 was measured by green reagent method.

RESULTSIGF-1 (100 microg/L) increased cell number and MD activity by 2.8-3.8 fold. WT markedly inhibited VSMC proliferation and completely abolished the above effects of IGF-1. IGF-1 inhibited PTEN activity in a concentration-(10-100 microg/L) and time--(3 min-24 h) dependent manner (P < 0.01).

CONCLUSIONIGF-1 increases VSM proliferation by increasing PI3K activity and inhibiting PTEN activity.