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首页> 外文期刊>BMC Genomics >Coordinated patterns of gene expressions for adult muscle build-up in transgenic mice expressing myostatin propeptide
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Coordinated patterns of gene expressions for adult muscle build-up in transgenic mice expressing myostatin propeptide

机译：表达肌生长抑制素原肽的转基因小鼠中成年肌肉堆积的基因表达的协调模式

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Background Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-β, plays a dominant role in the genetic control of muscle mass. Myostatin is synthesized as a precursor protein, which generates the N-terminal propeptide and the C-terminal mature myostatin peptide by a post-translational cleavage event. Previously, transgenic over-expression of myostatin propeptide in skeletal muscle results in significant muscle growth in early stages of development. The objectives of present study were to further characterize muscle growth in later stages of life and to identify genes and their expression patterns that are responsible for adult muscle build-up by myostatin propeptide. Results Immunohistochemical staining with an antibody to the N-terminus indicates a high level of myostatin propeptide present in the muscles of transgenic mice while there were no apparent differences in myostatin protein distribution in the muscle fibers between the transgenic and wild-type mice. Main individual muscles increased by 76–152% in the transgenic mice over their wild-type littermate mice at 12 months of age. A large number of nuclei were localized in the central and basal lamina of the myofibers in the transgenic mice as the number of nuclei per fiber and 100 μm2 area was significantly higher in transgenic mice than wild-type mice. By systemic comparisons of global mRNA expression patterns between transgenic mice and wild-type littermates using microarray and qRT-PCR techniques, we have identified distinct gene expression patterns to support adult muscle build-up by myostatin propeptide, which are comprised of enhanced expressions of myogenic regulatory factors and extracelullar matrix components, and differentially down-regulated expressions of genes related to protein degradation and mitochondrial ATP synthesis. Conclusion The results present a coordinated pattern of gene expressions for reduced energy utilization during muscle build-up in adult stage. Enhanced muscle buildup by myostatin propeptide is sustained by reduced ATP synthesis as a result of a decreased activity of protein degradation. Myostatin propeptide may have a therapeutic application to the treatment of clinical muscle wasting problems by depressing myostatin activity.
机译：背景骨骼肌的生长和维持对人体健康至关重要。肌肉调节基因之一，即肌生长抑制素，一种转化生长因子-β，在肌肉质量的遗传控制中起着主导作用。肌生长抑制素被合成为前体蛋白，其通过翻译后切割事件产生N端前肽和C端成熟的肌生长抑制素肽。以前，肌生长抑制素前肽在骨骼肌中的转基因过表达导致发育早期的显着肌肉生长。本研究的目的是进一步表征生命后期的肌肉生长，并鉴定基因和它们的表达模式，这些基因及其表达模式由肌生长抑制素原肽构成。结果用抗N末端抗体进行的免疫组织化学染色表明，转基因小鼠肌肉中存在高水平的肌肉生长抑制素原肽，而在转基因小鼠和野生型小鼠之间，肌肉生长抑制素蛋白分布没有明显差异。转基因小鼠在12个月大时，其主要个体肌肉比其野生型同窝小鼠增加了76–152％。转基因小鼠中大量核位于肌纤维的中央和基底层，因为转基因小鼠中每根纤维和100μm 2 区域的核数显着高于野生型小鼠。通过使用微阵列和qRT-PCR技术对转基因小鼠和野生型同窝仔之间的全局mRNA表达模式进行系统比较，我们已经确定了不同的基因表达模式来支持成肌生长素原肽增强成年肌肉的积累，其中包括成肌原性表达的增强调节因子和胞外基质成分，以及与蛋白质降解和线粒体ATP合成相关的基因的差异表达下调。结论结果表明，成年阶段肌肉堆积过程中基因表达的协调模式可减少能量利用。由于蛋白质降解活性的降低，ATP合成减少可维持肌肉生长抑制素原肽增强的肌肉堆积。肌生长抑制素原肽可以通过抑制肌生长抑制素活性来治疗临床上的肌肉萎缩问题。

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