The Internal Region Leucine-rich Repeat 6 of Decorin Interacts with Low Density Lipoprotein Receptor-related Protein-1, Modulates Transforming Growth Factor (TGF)-β-dependent Signaling, and Inhibits TGF-β-dependent Fibrotic Response in Skeletal Muscles
The Internal Region Leucine-rich Repeat 6 of Decorin Interacts with Low Density Lipoprotein Receptor-related Protein-1, Modulates Transforming Growth Factor (TGF)-β-dependent Signaling, and Inhibits TGF-β-dependent Fibrotic Response in Skeletal Muscles
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DOI：
10.1074/jbc.m111.312488
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发表时间：
2012-02-24
影响因子：
4.8
通讯作者：
Brandan, Enrique
中科院分区：
文献类型：
--
作者：
Cabello-Verrugio, Claudio;Santander, Cristian;Brandan, Enrique
Decorin是一种小的蛋白聚糖，由12个富含亮氨酸的重复序列（lrr）组成，它调节转化生长因子（tgf - β）和其他生长因子的活性，从而影响多种生理和病理过程中的增殖和分化，如纤维化，在一些组织和器官中。之前我们描述了两种新的tgf - β依赖性信号通路调节剂：LDL受体相关蛋白（LRP-1）和decorin。在这里，我们已经确定了decorin中负责与LRP-1相互作用并参与tgf - β依赖性结合和信号传导的区域。具体来说，我们使用了decorin缺失突变体，以及来自内部LRR区域的肽，来确定负责这些decorin功能的LRR。我们的研究结果表明，LRR6和LRR5参与与LRP-1和tgf - β的相互作用以及其依赖的信号传导。此外，内部区域（LRR6i）由11个氨基酸组成，负责decorin与LRP-1结合以及随后的tgf - β依赖性信号传导。此外，使用体内方法，我们还证明了decorin的LRR6区域可以抑制骨骼肌损伤中tgf - β介导的作用。
Decorin is a small proteoglycan, composed of 12 leucine-rich repeats (LRRs) that modulates the activity of transforming growth factor type beta (TGF-beta) and other growth factors, and thereby influences proliferation and differentiation in a wide array of physiological and pathological processes, such as fibrosis, in several tissues and organs. Previously we described two novel modulators of the TGF-beta-dependent signaling pathway: LDL receptor-related protein (LRP-1) and decorin. Here we have determined the regions in decorin that are responsible for interaction with LRP-1 and are involved in TGF-beta-dependent binding and signaling. Specifically, we used decorin deletion mutants, as well as peptides derived from internal LRR regions, to determine the LRRs responsible for these decorin functions. Our results indicate that LRR6 and LRR5 participate in the interaction with LRP-1 and TGF-beta as well as in its dependent signaling. Furthermore, the internal region (LRR6i), composed of 11 amino acids, is responsible for decorin binding to LRP-1 and subsequent TGF-beta-dependent signaling. Furthermore, using an in vivo approach, we also demonstrate that the LRR6 region of decorin can inhibit TGF-beta mediated action in response to skeletal muscle injury.