The insulin-like growth factor (IGF)-I E-peptides are required for isoform-specific gene expression and muscle hypertrophy after local IGF-I production
The insulin-like growth factor (IGF)-I E-peptides are required for isoform-specific gene expression and muscle hypertrophy after local IGF-I production
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DOI：
10.1152/japplphysiol.01308.2009
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发表时间：
2010-05-01
影响因子：
3.3
通讯作者：
Lei, Hanqin
中科院分区：
文献类型：
--
作者：
Barton, Elisabeth R.;DeMeo, J.;Lei, Hanqin
放大图片作者：巴顿ER，DeMeo J.胰岛素样生长因子（IGF）-I E-肽是局部IGF-I产生后亚型特异性基因表达和肌肉肥大所必需的。J Appl Physiol 108：1069-1076，2010.首次发表于2010年2月4日; doi：10.1152/japplphysiol.01308.2009。胰岛素样生长因子I（IGF-I）在多种细胞类型中协调增殖和分化。igf 1基因不仅产生IGF-I，而且通过选择性剪接产生多个羧基末端延伸，即E肽，从而产生不同的亚型。目前尚不清楚IGF-I同工型是否具有共同的作用途径，或者每种蛋白质是否具有特定的作用。病毒给予鼠IGF-IA、IGF-IB和缺乏E-肽延伸的成熟IGF用于鉴定年轻生长小鼠肌肉中的IGF-I同种型特异性应答基因。微阵列分析显示，无论是否存在E肽（如Bcl-XL），IGF-I的增加都会引起反应。相反，在病毒递送IGF-IA或IGF-IB（包括基质金属蛋白酶13（MMP 13））后观察到不同的表达模式。当将IGF-I同种型病毒给药至肌肉纤维上缺乏功能性IGF-I受体的MKR小鼠的肌肉中时，Bcl-XL的表达被阻止。然而，在病毒注射IGF-IB后，MMP 13表达在相同条件下持续存在。在4个月后病毒交付，表达IGF-IA或IGF-IB促进肌肉肥大，但病毒交付成熟的IGF-I未能增加肌肉质量。这些研究提供的证据表明，IGF-I的局部产生需要E-肽来驱动生长中的肌肉肥大，并且IGF-I同种型存在共同和独特的途径来促进生物学效应。
Barton ER, DeMeo J, Lei H. The insulin-like growth factor (IGF)-I E-peptides are required for isoform-specific gene expression and muscle hypertrophy after local IGF-I production. J Appl Physiol 108: 1069-1076, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01308.2009.-Insulin-like growth factor I (IGF-I) coordinates proliferation and differentiation in a wide variety of cell types. The igf1 gene not only produces IGF-I, but also generates multiple carboxy-terminal extensions, the E-peptides, through alternative splicing leading to different isoforms. It is not known if the IGF-I isoforms share a common pathway for their actions, or if there are specific actions of each protein. Viral administration of murine IGF-IA, IGF-IB, and mature IGF, which lacked an E-peptide extension, was utilized to identify IGF-I isoform-specific responsive genes in muscles of young growing mice. Microarray analysis revealed responses that were driven by increased IGF-I regardless of the presence of E-peptide, such as Bcl-XL. In contrast, distinct expression patterns were observed after viral delivery of IGF-IA or IGF-IB, which included matrix metalloproteinase 13 (MMP13). Expression of Bcl-XL was prevented when viral administration of the IGF-I isoforms was performed into muscles of MKR mice, which lack functional IGF-I receptors on the muscle fibers. However, MMP13 expression persisted under the same conditions after viral injection of IGF-IB. At 4 mo after viral delivery, expression of IGF-IA or IGF-IB promoted muscle hypertrophy, but viral delivery of mature IGF-I failed to increase muscle mass. These studies provide evidence that local production of IGF-I requires the E-peptides to drive hypertrophy in growing muscle and that both common and unique pathways exist for the IGF-I isoforms to promote biological effects.