期刊
NEUROMUSCULAR DISORDERS
卷 22, 期 12, 页码 1057-1068出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2012.07.002
关键词
Decorin; Small leucine rich proteoglycans; Myostatin; Skeletal muscle; Muscular dystrophy; mdx mouse
Decorin is a member of the small leucine-rich proteoglycan family and it is a component of the extracellular matrix. Decorin was previously shown to bind different molecules, including myostatin, in a zinc-dependent manner. Here, we investigated in detail the anti-myostatin activity of decorin and fragments thereof. We show that this protein displays in vitro anti-myostatin activities with an IC50 of 2.3 x 10(-8) M. After intramuscular injection of decorin in dystrophic mdx and gamma-sarcoglycan(-/-) mice, we observed a significant increase of the muscle mass and this effect was maximal 18 days after administration. Further, we show that the myostatin-binding site is located in the N-terminal domain of decorin. In fact, a peptide encompassing the 31-71 sequence retains full myostatin binding capacity and intramuscular injection of the peptide induces muscle hypertrophy. The evaluation of three additional peptides suggests a crucial role of the four cysteines within the conserved CX3CXCX6C motif of class I of the small leucine-rich proteoglycans. Altogether, our results show that the N-terminal domain of decorin is sufficient for the binding to myostatin and they underscore the crucial role for this interaction of zinc and the cysteine cluster. (C) 2012 Elsevier B.V. All rights reserved.
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