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首页> 外文期刊>Journal of Cellular Physiology >Myostatin negatively regulates the expression of the steroid receptor co-factor ARA70.
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Myostatin negatively regulates the expression of the steroid receptor co-factor ARA70.

机译：肌肉生长抑制素负调节的表达类固醇受体辅助因子ARA70。

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摘要

Myostatin is a transforming growth factor-beta (TGF-beta) superfamily member and a key negative regulator of embryonic and postnatal muscle growth. In order to identify downstream target genes regulated by Myostatin, we performed suppressive subtraction hybridization (SSH) on cDNA generated from the biceps femoris muscle of wild-type and myostatin-null mice. Sequence analysis identified several known and unknown genes as Myostatin downstream target genes. Here, we have investigated the regulation of gene expression of an androgen receptor (AR) binding co-factor, androgen receptor associated protein-70 (ARA70), by Myostatin. We show that in mouse there are two isoforms of ARA70 with high homology (79%) to human ARA70; an alpha-isoform which is a canonical ARA70 and a beta-isoform which has a 9 consecutive amino acid deletion and 6 amino acid substitutions in the carboxyl-terminal portion. Reverse Northern analysis on the differentially expressed cDNA library indicated that there is increased expression of ARA70 in the muscles of myostatin-null mice. In addition, Northern blot, together with semi-quantitative PCR analysis, confirmed that there is increased expression of ARA70 in myostatin-null biceps femoris muscle when compared to wild-type muscle. In corroboration of these results, addition of exogenous Myostatin results in down-regulation of ARA70 expression confirming that Myostatin is a negative regulator of ARA70 gene expression. Expression analysis further confirmed that ARA70 is up-regulated during myogenesis and that peak expression of ARA70 is observed following the peak expression of MyoD in differentiating myoblasts. Given that lack of Myostatin and increased expression of AR leads to hypertrophy, we propose that absence of Myostatin, at least in part, induces the hypertrophy phenotype by increasing the activity of AR by up-regulating the expression of ARA70, a known stimulating co-factor of AR.
机译：肌肉生长抑制素是一种改变的生长因子(及)超家族成员和负的关键监管机构的胚胎及产后肌肉增长。由肌肉生长抑制素基因,我们执行抑制的减法杂交(SSH)互补脱氧核糖核酸的股二头肌肌肉生成野生型和myostatin-null老鼠。分析确定了若干已知和未知肌肉生长抑制素基因下游靶基因。我们已经调查了基因的调控表达雄激素受体(AR)的绑定辅助因子,雄激素受体相关肌肉生长抑制素蛋白- 70 (ARA70)。鼠标有两种亚型ARA70高人类ARA70同源性(79%);这是一个典型ARA70和beta-isoform连续9个氨基酸缺失和6个氨基酸替换羧基末端部分。分析差异表达的互补库表示,有增加表达ARA70的肌肉myostatin-null老鼠。与半定量PCR分析,确认的表达增加在myostatin-null ARA70股二头肌肌肉与野生型相比,肌肉。这些结果证实,添加外生肌肉生长抑制素下调的结果ARA70确认肌肉生长抑制素是一种表达ARA70基因表达的负面调节器。表达分析进一步证实ARA70肌细胞生成,高峰期间上调表达ARA70后观察峰MyoD的微分表达式成肌细胞。AR的表达增加导致肥大,我们建议缺乏肌肉生长抑制素的,至少在部分,引起肥大表型增加活动调控的基于“增大化现实”技术ARA70的表达,一个已知的刺激基于“增大化现实”技术的辅助因子。

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