Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA 94121, USA.
Biochem Biophys Res Commun. 2010 May 28;396(2):219-23. doi: 10.1016/j.bbrc.2010.04.067. Epub 2010 Apr 14.
Previous work has suggested that an extracellular matrix degrading enzyme-matrix metalloproteinase-2 (MMP-2) plays an important role in the development of muscle atrophy. However, the transcriptional regulation mechanism of MMP-2 in skeletal muscle atrophy remains largely unknown. Using transgenic MMP-2 promoter reporter mice, we have demonstrated that AP-1 and RE-1 binding sites in the MMP-2 promoter region, coupled with increased binding of Fra-1, Fra-2 and AP-2, play a critical role in MMP-2 transcriptional regulation in muscle atrophy. Novel information gained from this study has improved our understanding of in vivo transcriptional regulation of MMP-2 in skeletal muscle atrophy.
先前的研究表明,细胞外基质降解酶——基质金属蛋白酶-2(MMP-2)在肌肉萎缩的发生发展中发挥着重要作用。然而,MMP-2 在骨骼肌萎缩中的转录调控机制在很大程度上仍不清楚。本研究利用 MMP-2 启动子报告基因转基因小鼠证实,MMP-2 启动子区域中的 AP-1 和 RE-1 结合位点,以及 Fra-1、Fra-2 和 AP-2 结合的增加,在肌肉萎缩时 MMP-2 的转录调控中起着关键作用。本研究获得的新信息增进了我们对 MMP-2 在骨骼肌萎缩中体内转录调控的理解。