Specific, temporally regulated expression of the insulin-like growth factor II gene during muscle cell differentiation.

Specific, temporally regulated expression of the insulin-like growth factor II gene during muscle cell differentiation.
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DOI:
10.1210/endo.133.2.8393762
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发表时间:
1993-08
期刊:
影响因子:
4.8
通讯作者:
K. Rosen;B. Wentworth;N. Rosenthal;L. Villa-komaroff
K. Rosen;B. Wentworth;N. Rosenthal;L. Villa-komaroff
中科院分区:
医学2区
文献类型:
--
作者:
K. Rosen;B. Wentworth;N. Rosenthal;L. Villa-komaroff

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我们将胰岛素样生长因子 II (IGF-II) 信使 RNA (mRNA) 的表达与编码已知在连续培养、融合的肌肉细胞系分化过程中发挥关键作用的蛋白质的其他 mRNA 的表达进行了比较。这些细胞系通过经历特征明确的基因表达改变来响应培养条件的变化,导致其表型从分裂的单核成肌细胞转变为融合的多核肌管。这种分化程序的标志包括诱导生肌调节基因以及编码收缩蛋白的基因。我们发现这些细胞的分化导致多种 IGF-II 转录物的产生。在所研究的细胞系之一中,C2C12、IGF-II mRNA 水平在分化过程中迅速诱导。 IGF-II mRNA 水平的增加先于收缩蛋白基因的表达,但仅在生肌调节基因肌细胞生成素激活后发生。在该细胞系的快速和缓慢融合亚克隆中观察到相同的 IGF-II mRNA 表达调节模式,表明肌肉分化过程中的特定点需要 IGF-II。这些结果表明IGF-II在骨骼肌细胞的终末分化过程中发挥重要作用,并且与自分泌环的存在相一致,IGF-II可以通过该自分泌环调节分化过程。
We have compared the expression of insulin-like growth factor II (IGF-II) messenger RNA (mRNA) to the expression of other mRNAs encoding proteins known to play pivotal roles during the differentiation of continuously cultured, fusing muscle cell lines. These cell lines respond to changes in culture conditions by undergoing a well characterized alteration in gene expression which leads to a change in their phenotype from dividing, mononucleate myoblasts to fused, multinucleate myotubes. The hallmarks of this differentiation program include the induction of myogenic regulatory genes as well as the genes that encode the contractile proteins. We have found that the differentiation of these cells leads to the production of multiple IGF-II transcripts. In one of the cell lines studied, C2C12, IGF-II mRNA levels were rapidly induced during differentiation. Increases in IGF-II mRNA levels preceded the expression of the contractile protein genes but occurred only after the activation of the myogenic regulatory gene myogenin. The same regulated pattern of IGF-II mRNA expression was seen in both rapidly and slowly fusing subclones of this cell line, indicating a requirement for IGF-II at a specific point during muscle differentiation. These results suggest that IGF-II plays an important role during the terminal differentiation of skeletal muscle cells and are consistent with the existence of an autocrine loop through which IGF-II may act to regulate the differentiation process.