A New Role for Sterol Regulatory Element Binding Protein 1 Transcription Factors in the Regulation of Muscle Mass and Muscle Cell Differentiation
A New Role for Sterol Regulatory Element Binding Protein 1 Transcription Factors in the Regulation of Muscle Mass and Muscle Cell Differentiation
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DOI：
10.1128/mcb.00690-09
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发表时间：
2010-03-01
影响因子：
5.3
通讯作者：
Lefai, Etienne
中科院分区：
文献类型：
--
作者：
Lecomte, Virginie;Meugnier, Emmanuelle;Lefai, Etienne
转录因子固醇调节元件结合蛋白1a（SREBP-1a）和SREBP-1c在胆固醇和脂肪酸代谢调节中的作用已得到充分研究;然而，对其在肌肉中的特定功能知之甚少。在本研究中，最近的微阵列数据分析过表达SREBP 1的肌肉细胞表明，他们可能发挥作用，在肌肉发生的调节。然后，我们证明了SREBP-1a和-1c抑制成肌细胞向肌管的分化，并且还诱导体内和体外肌肉萎缩。此外，我们已经确定了转录抑制因子BHLHB 2和BHLHB 3作为SREBP-1a和-1c在肌肉中的这些作用的介导剂。这两种阻遏物都是SREBP-1的靶基因，它们影响许多参与肌生成程序的基因的表达。我们的发现确定了SREBP-1转录因子在肌肉中的新作用，从而将肌肉质量的控制与代谢途径联系起来。
The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.