Badesch D B, Lee P D, Parks W C, Stenmark K R
Pulmonary Division, University of Colorado Health Sciences Center, Denver.
Biochem Biophys Res Commun. 1989 Apr 14;160(1):382-7. doi: 10.1016/0006-291x(89)91667-7.
Insulin-like growth factor I stimulates mitogenesis in smooth muscle cells, and upregulates elastin synthesis in embryonic aortic tissue. Increased smooth muscle elastin synthesis may play an important role in vascular remodeling in chronic pulmonary hypertension. Therefore, we studied the effect of IGF-I on elastin and total protein synthesis by pulmonary arterial smooth muscle cells in vitro. Tropoelastin synthesis was measured by enzyme immunoassay, and total protein synthesis was measured by [3H]-leucine incorporation. In addition, the steady-state levels of tropoelastin mRNA were determined by slot blot hybridization. Incubation of confluent cultures with various concentrations of IGF-I resulted in a dose-dependent stimulation of elastin synthesis, with a 2.4-fold increase over control levels at 1000 ng/ml of IGF. The increase in elastin synthesis was reflected by a stimulation of the steady-state levels of tropoelastin mRNA. We conclude that IGF-I has potent elastogenic effects on vascular smooth muscle cells, and speculate that it may contribute to vascular wall remodeling in chronic hypertension.
胰岛素样生长因子I刺激平滑肌细胞的有丝分裂，并上调胚胎主动脉组织中的弹性蛋白合成。平滑肌弹性蛋白合成增加可能在慢性肺动脉高压的血管重塑中起重要作用。因此，我们在体外研究了IGF-I对肺动脉平滑肌细胞弹性蛋白和总蛋白合成的影响。通过酶免疫测定法测量原弹性蛋白合成，通过[3H]-亮氨酸掺入法测量总蛋白合成。此外，通过狭缝印迹杂交法测定原弹性蛋白mRNA的稳态水平。用不同浓度的IGF-I孵育汇合培养物导致弹性蛋白合成呈剂量依赖性刺激，在1000 ng/ml的IGF时比对照水平增加2.4倍。弹性蛋白合成的增加反映在原弹性蛋白mRNA稳态水平的刺激上。我们得出结论，IGF-I对血管平滑肌细胞具有强大的弹性生成作用，并推测它可能有助于慢性高血压中的血管壁重塑。
