Regulation of insulin-like growth factor-I gene expression by growth factors in cultured vascular smooth muscle cells

Abstract

The aim of this investigation was to study the regulation of insulin-like growth factor-I (IGF-I) gene expression in cultured rat aortic smooth muscle cells. Near-confluent cells were deprived of serum for 24 h and then exposed to IGF-I, insulin, serum, basic fibroblast growth factor (basic FGF), platelet-derived growth factor (PDGF-BB; consisting of B-chain homodimer) or GH for 24 h. Levels of IGF-I mRNA were measured by solution hybridization. The level of IGF-I mRNA was markedly decreased by 10% (v/v) newborn calf serum (78 +/- 4 (S.E.M.) % decrease), 1 nmol basic FGF/l (53 +/- 8%), and 1 nmol PDGF-BB/l (40 +/- 3%) when measured after 24 h. The effect of PDGF-BB was significant after 6 h and became more marked after 24 h. GH (1 nmol/l or 0.1 mumol/l) or insulin (1 nmol/l) had no effect after 24 h, whereas IGF-I (1 nmol/l) and insulin (10 mumol/l) increased IGF-I mRNA 64 +/- 20% and 46 +/- 14% respectively. The increase caused by IGF-I was demonstrated after 3 h, and was most marked after 24 h. Using Northern blot analysis of cultured aortic smooth muscle cells, IGF-I transcripts of 7.4, 1.7 and 1.1-0.8 kilobases were observed. Exposure of the cells to 10% serum, 1 nmol basic FGF/l or 1 nmol PDGF-BB/l for 48 h increased the cell number by 104 +/- 7%, 64 +/- 3% and 61 +/- 22% respectively, while IGF-I, insulin and GH had little effect.(ABSTRACT TRUNCATED AT 250 WORDS)