Tan E M, Dodge G R, Sorger T, Kovalszky I, Unger G A, Yang L, Levine E M, Iozzo R V
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Lab Invest. 1991 Apr;64(4):474-82.
We have previously shown that human vascular smooth muscle cells grown for several passages in the presence of heparin and endothelial cell growth factor (ECGF) exhibit profound alterations in the synthesis of extracellular matrix proteins. In the present study, we demonstrate that the mRNA steady-state levels for various matrix macromolecules were altered in the presence of heparin and ECGF, but not ECGF alone. Specifically, the expression of types I and IV collagens, fibronectin, and decorin proteoglycan genes were markedly inhibited, whereas that of versican proteoglycan and beta-actin genes were unaffected. The effects were fully reversible. The suppression of the collagen gene expression was related to decreased collagen production by cells incubated with heparin and ECGF. Thus, heparin and ECGF synergistically elicit a coordinate and selective inhibition of matrix gene expression in human smooth muscle cells.
我们先前已表明，在肝素和内皮细胞生长因子（ECGF）存在的情况下培养数代的人血管平滑肌细胞，其细胞外基质蛋白合成表现出深刻变化。在本研究中，我们证明，在肝素和ECGF存在时，各种基质大分子的mRNA稳态水平发生了改变，但单独使用ECGF时则未改变。具体而言，I型和IV型胶原、纤连蛋白和核心蛋白聚糖基因的表达受到显著抑制，而多功能蛋白聚糖和β-肌动蛋白基因的表达未受影响。这些影响是完全可逆的。胶原基因表达的抑制与用肝素和ECGF孵育的细胞中胶原产生的减少有关。因此，肝素和ECGF协同引发对人平滑肌细胞中基质基因表达的协同和选择性抑制。
