Expression profile of IGF paralog genes in liver and muscle of a GH-transgenic zebrafish
Expression profile of IGF paralog genes in liver and muscle of a GH-transgenic zebrafish
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DOI：
10.1016/j.ygcen.2015.12.017
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发表时间：
2016-01-15
影响因子：
2.7
通讯作者：
Marins, Luis Fernando
中科院分区：
文献类型：
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作者：
Nornberg, Bruna Felix;Figueiredo, Marcio Azevedo;Marins, Luis Fernando
本研究的目的是调查胰岛素样生长因子在肝脏和骨骼肌与肌肉肥大先前观察到的生长激素转基因斑马鱼线之间的关系。从这个意义上讲，我们评估了与IGF系统相关的基因在转基因动物肝脏和肌肉中的表达，以及GH/IGF轴所使用的主要细胞内信号通路。我们的研究结果表明，igf 1a，igf 2a和igf 2b基因在肝脏中的表达增加。此外，有一个减少igf 1 ra的表达和增加肌肉igf 2 r的转基因，表明肌肉组织的负响应相对于过量的循环IGF。肌肉IGFs表达分析显示，只有igf 2b的显着增加，伴随着一个平行的诱导igfbp 5a基因。IGFBP 5a的存在可增强IGF 2在肌细胞分化中的作用。关于JAK/STAT相关基因，我们观察到stat 3和stat 5a在转基因鱼肝脏中的表达谱的改变。在肌肉中没有观察到任何变化，这表明这两种组织对GH转基因的反应不同。蛋白质印迹分析表明增殖（MEK/ERK）和肥大（PI 3 K/Akt）途径的磷酸化水平之间不平衡，有利于后者。总之，本研究的结果表明，在斑马鱼GH转基因引起的肥大可能是由于循环IGF由肝脏产生，肌肉IGF 2b的重要参与。这组IGFs似乎有利于转基因斑马鱼肌肉组织中的肥大细胞内途径。(C)2015 Elsevier Inc. All rights reserved.
The objective of this study was to investigate the relationship between IGFs produced in the liver and skeletal muscle with muscle hypertrophy previously observed in a line of GH-transgenic zebrafish. In this sense, we evaluated the expression of genes related to the IGF system in liver and muscle of transgenics, as well as the main intracellular signaling pathways used by GH/IGF axis. Our results showed an increase in expression of igf1a, igf2a, and igf2b genes in the liver. Moreover, there was a decrease in the expression of igf1ra and an increase in muscle igf2r of transgenics, indicating a negative response of muscle tissue with respect to excess circulating IGFs. Muscle IGFs expression analyses revealed a significant increase only for igf2b, accompanied by a parallel induction of igfbp5a gene. The presence of IGFBP5a may potentiate the IGF2 action in muscle cells differentiation. Regarding JAK/STAT-related genes, we observed an alteration in the expression profile of both stat3 and stat5a in transgenic fish liver. No changes were observed in the muscle, suggesting that both tissues respond differently to GH-transgenesis. Western blotting analyses indicated an imbalance between the phosphorylation levels of the proliferative (MEK/ERK) and hypertrophic (PI3K/Akt) pathways, in favor of the latter. In summary, the results of this study suggest that the hypertrophy caused by GH-transgenesis in zebrafish may be due to circulating IGFs produced by the liver, with an important participation of muscle IGF2b. This group of IGFs appears to be favoring the hypertrophic intracellular pathway in muscle tissue of transgenic zebrafish. (C) 2015 Elsevier Inc. All rights reserved.