Li Yong, Li Juan, Zhu Jinghong, Sun Bin, Branca Maria, Tang Ying, Foster William, Xiao Xiao, Huard Johnny
Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Mol Ther. 2007 Sep;15(9):1616-22. doi: 10.1038/sj.mt.6300250. Epub 2007 Jul 3.
We have shown that decorin, a small leucine-rich proteoglycan, can inhibit transforming growth factor (TGF)-beta1 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 up-regulation of follistatin, peroxisome-proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha), p21, and the myogenic genes, and the down-regulation of TGF-beta1 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.
我们已经证明，核心蛋白聚糖（一种富含亮氨酸的小分子蛋白聚糖）能够抑制转化生长因子（TGF）-β1，从而防止纤维瘢痕形成，并改善损伤后肌肉的愈合。在经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增强。在本文中，我们报告了关于核心蛋白聚糖是否对成肌细胞分化有直接影响的研究结果。我们的结果表明，经基因工程改造以表达核心蛋白聚糖的成肌细胞（CD细胞）分化为肌管的速率显著高于对照成肌细胞（C2C12）。这种增强的分化导致体外CD细胞中成肌基因（Myf5、Myf6、MyoD和肌细胞生成素）上调。我们推测，CD细胞表现出较高分化速率的原因是卵泡抑素、过氧化物酶体增殖物激活受体-γ共激活因子-1α（PGC-1α）、p21和成肌基因的上调，以及TGF-β1和肌肉生长抑制素的下调。体内核心蛋白聚糖基因转移促进了骨骼肌再生，并加速了损伤后肌肉的愈合。这些结果表明，核心蛋白聚糖不仅能防止纤维化，还能改善肌肉再生和修复。
