REGULATION OF INSULIN-LIKE GROWTH FACTOR-I MESSENGER-RNA LEVELS IN VASCULAR SMOOTH-MUSCLE CELLS

We have previously demonstrated specific insulin-like growth factor I (IGF I) messenger RNA (mRNA) transcripts in cultured rat aortic smooth muscle cells (RASM). To define the role of IGF I in the autocrine growth program of vascular smooth muscle cells, we quantitated IGF I mRNA levels in proliferating and quiescent (serum-deprived for 48 hours) RASM. IGF I mRNA levels were markedly decreased in quiescent cells, and this effect was reversible on reexposure to serum. Since platelet-derived growth factor (PDGF) acts synergistically with IGF I to stimulate vascular smooth muscle cell growth, we exposed quiescent RASM to PDGF AB or BB and quantitated IGF I transcript levels. Both PDGF dimers caused a marked, rapid increase in IGF I message levels. To determine whether induction of IGF I mRNA levels correlated with secretion of IGF I, we measured immunoreactive IGF I in RASM conditioned medium after separation of IGF I binding proteins by gel filtration chromatography. PDGF caused a significant increase in IGF I release at 24 hours. These findings indicate that IGF I mRNA levels in vitro are regulated by serum and by growth factors such as PDGF. Serum deprivation reversibly decreases IGF I transcript levels, and exposure of quiescent cells to PDGF increases IGF I mRNA levels and IGF I release. Regulation of IGF I expression by competence growth factors such as PDGF may play an important role in the control of vascular smooth muscle cell growth.