Clemmons D R
J Cell Physiol. 1984 Nov;121(2):425-30. doi: 10.1002/jcp.1041210222.
Multiple growth factors that circulate in plasma have been shown to stimulate cellular growth in vitro. The plasma growth factors appear to stimulate DNA synthesis in cultured fibroblasts only after prior exposure of cell growth factors derived from circulating cell types, such as platelets and macrophages. The purpose of these studies was to investigate the role of the plasma growth factors in stimulating smooth muscle cell replication following exposure to platelet-derived growth factor (PDGF). Following transient exposure to PDGF, insulin stimulated smooth muscle cell replication but only when supraphysiologic concentrations were used (i.e., greater than 1.0 micrograms/ml). Somatomedin-C (Sm-C), in contrast, was found to stimulate a 320% increase in [3H]thymidine incorporation when concentrations that are present in extracellular fluids were used (i.e., 0.5-10 ng/ml). Epidermal growth factor (EGF), an important mitogen for multiple cell types, caused a 70% increase in [3H]thymidine incorporation when added to quiescent cells following PDGF exposure, and EGF caused a substantial increase in the absolute level of [3H]thymidine incorporation when coincubated with Sm-C. When EGF (1 ng/ml) was incubated simultaneously with concentrations of Sm-C between 1 and 10 ng/ml plus Sm-C-deficient plasma, maximal [3H]thymidine incorporation was 2.1-fold greater in the presence of EGF. In contrast, insulin (20 ng/ml), when coincubated with Sm-C under similar conditions, had no enhancing effect on the cellular response to Sm-C. None of the plasma factors tested was an effective stimultant of replication when incubated either in serum-free medium or in the presence of Sm-C-deficient plasma without prior PDGF exposure. Hydrocortisone was shown to inhibit smooth muscle cell replication in concentrations between 10(-7) and 10(-5) M. In summary, multiple plasma growth factors can stimulate the smooth muscle cell replication, and Sm-C appears to be most effective of those tested. Insulin and EGF appear to work by different mechanisms; that is, EGF can facilitate the cellular response to Sm-C, whereas insulin is effective only at supraphysiologic concentrations at which it will directly bind to Sm-C receptors.
血浆中循环的多种生长因子已被证明可在体外刺激细胞生长。血浆生长因子似乎只有在事先接触了循环细胞类型（如血小板和巨噬细胞）衍生的细胞生长因子后，才会刺激培养的成纤维细胞中的DNA合成。这些研究的目的是探讨血浆生长因子在暴露于血小板衍生生长因子（PDGF）后刺激平滑肌细胞复制中的作用。短暂暴露于PDGF后，胰岛素可刺激平滑肌细胞复制，但仅在使用超生理浓度（即大于1.0微克/毫升）时才会如此。相比之下，当使用细胞外液中存在的浓度（即0.5 - 10纳克/毫升）时，生长调节素C（Sm - C）可刺激[3H]胸苷掺入量增加320%。表皮生长因子（EGF）是多种细胞类型的重要促有丝分裂原，在PDGF暴露后添加到静止细胞中时，可使[3H]胸苷掺入量增加70%，并且当与Sm - C共同孵育时，EGF可使[3H]胸苷掺入的绝对水平大幅增加。当EGF（1纳克/毫升）与浓度在1至10纳克/毫升之间的Sm - C以及缺乏Sm - C的血浆同时孵育时，在有EGF存在的情况下，最大[3H]胸苷掺入量增加了2.1倍。相比之下，胰岛素（20纳克/毫升）在类似条件下与Sm - C共同孵育时，对细胞对Sm - C的反应没有增强作用。在无血清培养基中孵育或在没有事先PDGF暴露的情况下在缺乏Sm - C的血浆存在下孵育时，所测试的血浆因子均不是有效的复制刺激剂。已表明氢化可的松在浓度为10^(-7)至10^(-5) M之间可抑制平滑肌细胞复制。总之，多种血浆生长因子可刺激平滑肌细胞复制，并且Sm - C在所测试的因子中似乎最有效。胰岛素和EGF似乎通过不同机制起作用；也就是说，EGF可促进细胞对Sm - C的反应，而胰岛素仅在超生理浓度下才有效，此时它会直接与Sm - C受体结合。
