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.
Delafontaine
P
P
Department of Medicine, Emory University, Atlanta, GA.
Lou
H
H
Alexander
R W
RW
D015152:Blotting, Northern; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D011863:Radioimmunoassay; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D012710:Serum Albumin, Bovine; D007334:Insulin-Like Growth Factor I