Transcriptional regulation of the IGF signaling pathway by amino acids and insulin-like growth factors during myogenesis in Atlantic salmon.
Transcriptional regulation of the IGF signaling pathway by amino acids and insulin-like growth factors during myogenesis in Atlantic salmon.
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DOI：
10.1371/journal.pone.0011100
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发表时间：
2010-06-14
期刊：
影响因子：
3.7
通讯作者：
Johnston IA
中科院分区：
文献类型：
--
作者：
Bower NI;Johnston IA
胰岛素样生长因子信号通路是骨骼肌生长的重要调节因子。我们研究了从大西洋鲑鱼(Salmo Salar)快速肌肉分离的原代细胞培养的肌管成熟过程中胰岛素样生长因子(IGF)信号通路各组成部分以及成纤维细胞生长因子2(FGF2)的mRNA表达。研究了氨基酸和胰岛素样生长因子对IGFS和IGFBP表达的转录调控。培养第2天和第3天细胞的增殖率为15%d−1，第6天细胞增殖率为66%d−1。在培养的成熟期，与单核细胞(IGFBP5.1和5.2、IGFBP-6、IGFBP-RP1、IGFBP-2.2和IGF-II)、增殖初期(IGFI、IGFBP-4、FGF2和IGFIRB)以及终末分化和肌管生成(IGF2R、IGF1RA)相关的基因表达均有上调。在氨基酸和血清饥饿72h的细胞中，IGF-I mRNA下降10倍，而氨基酸替代可逆转这一现象。在饥饿细胞中加入胰岛素样生长因子-I和氨基酸导致胰岛素样生长因子-I基因的表达增加18倍，这表明协同作用和激活额外的途径(S)通过正反馈机制导致胰岛素样生长因子-I的产生。IGF-II、IGFBP-5.1和IGFBP-5.2的表达在饥饿细胞中没有变化，但随着氨基酸的替代而增加。加入IGF-I、IGF-II或胰岛素和氨基酸后，IGFBP5.2和IGFBP-4的表达协同增加，而IGFBP5.1的表达无明显变化。IGF-I和IGF-II直接刺激IGFBP-6的表达，但在氨基酸存在的情况下不能。这些发现表明，仅氨基酸就足以刺激成肌细胞的肌肉生成，IGF-I的产生受内分泌和旁分泌途径的共同控制。提出了一个描述大西洋鲑鱼摄食后IGF途径转录调控的模型。
The insulin-like growth factor signalling pathway is an important regulator of skeletal muscle growth. We examined the mRNA expression of components of the insulin-like growth factor (IGF) signalling pathway as well as Fibroblast Growth Factor 2 (FGF2) during maturation of myotubes in primary cell cultures isolated from fast myotomal muscle of Atlantic salmon (Salmo salar). The transcriptional regulation of IGFs and IGFBP expression by amino acids and insulin-like growth factors was also investigated. Proliferation of cells was 15% d−1 at days 2 and 3 of the culture, increasing to 66% d−1 at day 6. Three clusters of elevated gene expression were observed during the maturation of the culture associated with mono-nucleic cells (IGFBP5.1 and 5.2, IGFBP-6, IGFBP-rP1, IGFBP-2.2 and IGF-II), the initial proliferation phase (IGF-I, IGFBP-4, FGF2 and IGF-IRb) and terminal differentiation and myotube production (IGF2R, IGF-IRa). In cells starved of amino acids and serum for 72 h, IGF-I mRNA decreased 10-fold which was reversed by amino acid replacement. Addition of IGF-I and amino acids to starved cells resulted in an 18-fold increase in IGF-I mRNA indicating synergistic effects and the activation of additional pathway(s) leading to IGF-I production via a positive feedback mechanism. IGF-II, IGFBP-5.1 and IGFBP-5.2 expression was unchanged in starved cells, but increased with amino acid replacement. Synergistic increases in expression of IGFBP5.2 and IGFBP-4, but not IGFBP5.1 were observed with addition of IGF-I, IGF-II or insulin and amino acids to the medium. IGF-I and IGF-II directly stimulated IGFBP-6 expression, but not when amino acids were present. These findings indicate that amino acids alone are sufficient to stimulate myogenesis in myoblasts and that IGF-I production is controlled by both endocrine and paracrine pathways. A model depicting the transcriptional regulation of the IGF pathway in Atlantic salmon muscle following feeding is proposed.
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影响因子：
4.8
作者：
COLEMAN, ME;DEMAYO, F;SCHWARTZ, RJ
通讯作者：
SCHWARTZ, RJ
影响因子：
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