IGF-II IS MORE ACTIVE THAN IGF-I IN STIMULATING L6A1 MYOGENESIS - GREATER MITOGENIC ACTIONS OF IGF-I DELAY DIFFERENTIATION
IGF-II IS MORE ACTIVE THAN IGF-I IN STIMULATING L6A1 MYOGENESIS - GREATER MITOGENIC ACTIONS OF IGF-I DELAY DIFFERENTIATION
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DOI：
10.1002/jcp.1041610212
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发表时间：
1994-11-01
影响因子：
5.6
通讯作者：
FLORINI, JR
中科院分区：
文献类型：
--
作者：
EWTON, DZ;ROOF, SL;FLORINI, JR
有丝分裂原通常被认为抑制肌肉生成，许多细胞生物学家发现很难解释胰岛素样生长因子（IGFs）在培养中刺激肌肉细胞的增殖和分化。我们之前的研究表明，I型IGF受体介导这些作用。然而，IGF-II和胰岛素治疗导致成肌细胞更广泛地分化，这表明可能涉及更复杂的机制。在这里，我们提出的证据表明，与ICF-II和胰岛素相比，IGF-I更大的有丝分裂活性会延迟L6A1成肌细胞的分化。在抑制IGF-I有丝分裂作用的条件下，ICF-I对肌生成的刺激接近IGF-II:(1)在较高细胞密度的L6A1培养物中；(2)在L6A1培养物中，细胞增殖被胞嘧啶阿拉伯糖苷或阿飞霉素抑制；(3)培养的原代人肌肉细胞对igf - 1表现出较小的有丝分裂反应。通过使用IGF-I和ICF-II类似物获得了I型受体在传递分化信号中起主要作用的进一步证据。对I型受体的亲和力降低的类似物活性急剧下降，而对II型受体的亲和力增加的类似物活性并不比天然IGF-I更活跃。我们的研究结果表明，igf - 1的有丝分裂和肌生成作用都是由I型受体介导的。我们得出的结论是，igf - 1由于其有丝分裂作用而延迟了肌生成的发生，并且仅在随后刺激肌生成。这些观察结果调和了我们的结果与igf和其他研究者关于其他有丝分裂原的影响的报告之间的明显冲突。(C) 1994 Wiley-Liss, Inc。
Mitogens are generally thought to inhibit myogenesis, and many cell biologists have found it hard to interpret observations that the insulin-like growth factors (IGFs) stimulate both proliferation and differentiation of muscle cells in culture. Our previous studies suggested that the Type I IGF receptor mediates these actions. However, IGF-II and insulin treatment caused myoblasts to differentiate much more extensively, suggesting that more complex mechanisms may be involved. Here we present evidence that the greater mitogenic activity of IGF-I (compared to ICF-II and insulin) delays L6A1 myoblast differentiation. Under conditions in which the mitogenic actions of IGF-I are suppressed, the stimulation of myogenesis by ICF-I approached that by IGF-II: (1) in L6A1 cultures plated at a higher cell density; (2) in L6A1 cultures in which cell proliferation was inhibited by cytosine arabinoside or aphidicolin; and (3) in cultures of primary human muscle cells, which exhibit a smaller mitogenic response to IGF-I. Further evidence that the Type I receptor plays a major role in relaying the signal for differentiation was obtained by using IGF-I and ICF-II analogs. Analogs which have reduced affinity for the Type I receptor showed a dramatic decrease in activity, while ananalog with increased affinity for the Type II receptor was no more active than native IGF-I. Our results indicate that both mitogenic and myogenic actions of IGF-I are mediated by the Type I receptor. We conclude that IGF-I delays the onset of myogenesis as a result of its mitogenic actions, and only subsequently stimulates myogenesis. These observations reconcile the apparent conflict between our results with the IGFs and other investigators' reports of effects of other mitogens. (C) 1994 Wiley-Liss, Inc.