Cercek B, Fishbein M C, Forrester J S, Helfant R H, Fagin J A
Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA 90048-0750.
Circ Res. 1990 Jun;66(6):1755-60. doi: 10.1161/01.res.66.6.1755.
Insulin-like growth factor I (IGF-I) is a widely distributed mitogen that mediates the growth-promoting effects of platelet-derived growth factor in mesenchymal cells. We show that rat aortic IGF-I messenger RNA (mRNA) is induced 24 hours after deendothelialization, at a time when smooth muscle cell proliferation within the intima is still not apparent. After 7 days, IGF-I mRNA induction peaks at about ninefold control levels and then falls to about threefold 14 days after denudation when smooth muscle cell proliferation is at its peak. We also show that, of the 5' untranslated IGF-I mRNA transcripts, only the class C transcript is expressed and regulated in aortic tissue. In contrast, treatment of rats with supraphysiological doses of growth hormone, the major endocrine regulator of IGF-I gene expression, elicited only twofold induction of aortic IGF-I mRNA. Our findings suggest that IGF-I may be an important autocrine or paracrine regulator of smooth muscle cell proliferation and that it may be significant in determining the cellular response to arterial wall injury.
胰岛素样生长因子I(IGF-I)是一种广泛分布的促有丝分裂原,可介导血小板衍生生长因子在间充质细胞中的促生长作用。我们发现,大鼠主动脉IGF-I信使核糖核酸(mRNA)在内皮剥脱后24小时被诱导,此时内膜平滑肌细胞增殖尚不明显。7天后,IGF-I mRNA诱导峰值约为对照水平的9倍,然后在剥脱后14天降至约3倍,此时平滑肌细胞增殖达到峰值。我们还发现,在5'非翻译IGF-I mRNA转录本中,只有C类转录本在主动脉组织中表达并受到调控。相比之下,用超生理剂量的生长激素(IGF-I基因表达的主要内分泌调节因子)处理大鼠,仅引起主动脉IGF-I mRNA两倍的诱导。我们的研究结果表明,IGF-I可能是平滑肌细胞增殖的重要自分泌或旁分泌调节因子,并且在确定细胞对动脉壁损伤的反应中可能具有重要意义。