Expression and regulation of insulin-like growth factor binding proteins in vascular smooth muscle cells

Insulin-like growth factor-I (IGF-I) plays an important role in regulating vascular smooth muscle cell (VSMC) proliferation, migration and apoptosis. The IGFs present in the extracellular environments are bound to members of a family of high-affinity binding proteins (IGFBPs). VSMCs secrete several IGFBPs including IGFBP-2, -4 and -5. These IGFBPs have been shown to either potentiate or inhibit the IGF-I actions in this cell type. In cultured VSMCs, IGF-I is a potent regulator of the availability of its own IGFBPs. IGF-I down-regulates IGFBP-4 levels by activating of IGFBP-4 proteolysis, whereas it up-regulates IGFBP-5 levels by stimulating the IGFBP-5 biosynthesis. IGF-I also has a moderate effect on the IGFBP-2 synthesis and proteolysis. Further dissection of the molecular interactions between IGF-I and IGFBPs will be important to our understanding of the cellular and molecular mechanisms underlying IGF-I action in VSMCs.