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AP-1 和 RE-1 结合位点在骨骼肌肉萎缩症中基质金属蛋白酶-2 转录调控中的作用。

Role of AP-1 and RE-1 binding sites in matrix metalloproteinase-2 transcriptional regulation in skeletal muscle atrophy.

机构信息

Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA 94121, USA.

出版信息

Biochem Biophys Res Commun. 2010 May 28;396(2):219-23. doi: 10.1016/j.bbrc.2010.04.067. Epub 2010 Apr 14.

Abstract

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.

摘要

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。

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