Tollefsen S E, Lajara R, McCusker R H, Clemmons D R, Rotwein P
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110.
J Biol Chem. 1989 Aug 15;264(23):13810-7.
The insulin-like growth factors (IGFs) I and II exert pleiotropic effects on diverse cell types through interaction with specific high affinity cell surface receptors and with locally produced binding proteins. In skeletal muscle and in myoblast cell lines, the functions of IGF-I and -II are complex. Both growth factors appear capable of stimulating cellular proliferation and differentiation, as well as exerting insulin-like effects on intermediary metabolism. We have demonstrated recently that the expression of IGF-II and its receptor is induced during the terminal differentiation of the myoblast cell line, C2, and have suggested that IGF-II may be an autocrine growth factor in these cells (Tollefsen, S.E., Sadow, J.L., and Rotwein, P. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 1543-1547). We now have examined this cell line for expression of other components involved in IGF signaling. The synthesis of IGF-I is low during myoblast proliferation; IGF-I mRNA can be detected only through use of a sensitive solution hybridization assay. Typical IGF-I receptors can be measured in myoblasts, whereas IGF binding proteins cannot be detected in proliferating cells or in conditioned culture medium. During myogenic differentiation, IGF-I mRNA levels increase transiently by 6-10-fold within 48-72 h. The expression of IGF-I mRNA is accompanied by a 2.5-fold accumulation of IGF-I in the culture medium. IGF-I receptors also increase transiently, doubling by 48 h after the onset of differentiation. By contrast, secretion of a Mr 29,000 IGF binding protein is induced 30-fold to 100 ng/ml within 16 h and continues to increase throughout differentiation. These studies demonstrate that several components critical to IGF action are produced in a fusing skeletal muscle cell line in a differentiation-dependent manner and suggest that both IGF-I and IGF-II may be autocrine factors for muscle.
胰岛素样生长因子（IGFs）I和II通过与特定的高亲和力细胞表面受体以及局部产生的结合蛋白相互作用，对多种细胞类型发挥多效性作用。在骨骼肌和成肌细胞系中，IGF-I和-II的功能很复杂。这两种生长因子似乎都能够刺激细胞增殖和分化，以及对中间代谢发挥胰岛素样作用。我们最近证明，IGF-II及其受体的表达在成肌细胞系C2的终末分化过程中被诱导，并提出IGF-II可能是这些细胞中的自分泌生长因子（托勒夫森，S.E.，萨多，J.L.，和罗特温，P.（1989年）美国国家科学院院刊86，1543 - 1547）。我们现在已经检测了该细胞系中参与IGF信号传导的其他成分的表达。在成肌细胞增殖过程中，IGF-I的合成量很低；只有通过使用灵敏的溶液杂交试验才能检测到IGF-I mRNA。在成肌细胞中可以检测到典型的IGF-I受体，而在增殖细胞或条件培养基中检测不到IGF结合蛋白。在成肌分化过程中，IGF-I mRNA水平在48 - 72小时内短暂增加6 - 10倍。IGF-I mRNA的表达伴随着培养基中IGF-I积累2.5倍。IGF-I受体也短暂增加，在分化开始后48小时增加一倍。相比之下，一种分子量为29,000的IGF结合蛋白的分泌在16小时内被诱导增加30倍至100 ng/ml，并在整个分化过程中持续增加。这些研究表明，对IGF作用至关重要的几种成分在融合的骨骼肌细胞系中以分化依赖的方式产生，并表明IGF-I和IGF-II都可能是肌肉的自分泌因子。
