Decorin gene transfer promotes muscle cell differentiation and muscle regeneration
Decorin gene transfer promotes muscle cell differentiation and muscle regeneration
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DOI：
10.1038/sj.mt.6300250
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发表时间：
2007-09-01
影响因子：
12.4
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Li, Yong;Li, Juan;Huard, Johnny
我们已经证明，核心蛋白聚糖，一种富含亮氨酸的小蛋白聚糖，可以抑制转化生长因子（TGF）-β 1，以防止纤维性瘢痕形成，并改善损伤后的肌肉愈合。在核心蛋白聚糖处理的肌肉中，通过组织学检查观察到肌肉再生的增强。在这篇文章中，我们报告了核心蛋白聚糖是否对肌原细胞的分化有直接影响的测定。我们的研究结果表明，基因工程表达核心蛋白聚糖的成肌细胞（CD细胞）分化成肌管的速度明显高于对照成肌细胞（C2 C12）。这种增强的分化导致体外CD细胞中肌生成基因（Myf 5、Myf 6、MyoD和肌生成素）的上调。我们推测，CD细胞表现出的较高分化率是由于卵泡抑素、过氧化物酶体增殖物激活受体-γ共激活因子-1 α（PGC-1 α）、p21和生肌基因的上调，以及TGF-β 1和肌生长抑制素的下调。核心蛋白聚糖基因转移促进骨骼肌再生，加速肌肉损伤后的愈合。这些结果表明，核心蛋白聚糖不仅可以防止纤维化，而且可以改善肌肉再生和修复。
We have shown that decorin, a small leucine-rich proteoglycan, can inhibit transforming growth factor ( TGF)-beta 1 to prevent fibrous scar formation and improve muscle healing after injury. In the decorin-treated muscle, an enhancement of muscle regeneration is observed through histological examination. In this article, we report our determination of whether decorin has a direct effect on myogenic cells' differentiation. Our results indicate that myoblasts genetically engineered to express decorin ( CD cells) differentiated into myotubes at a significantly higher rate than did control myoblasts ( C2C12). This enhanced differentiation led to the up-regulation of myogenic genes ( Myf5, Myf6, MyoD, and myogenin) in CD cells in vitro. We speculate that the higher rate of differentiation exhibited by the CD cells is due to the upregulation of follistatin, peroxisome-proliferator-activated receptor-gamma co-activator-1 alpha ( PGC-1 alpha), p21, and the myogenic genes, and the down-regulation of TGF-beta 1 and myostatin. Decorin gene transfer in vivo promoted skeletal muscle regeneration and accelerated muscle healing after injury. These results suggest that decorin not only prevents fibrosis but also improves muscle regeneration and repair.