Transforming growth factor-β1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle -: A key event in muscle fibrogenesis
Transforming growth factor-β1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle -: A key event in muscle fibrogenesis
复制标题
DOI：
10.1016/s0002-9440(10)63188-4
复制
发表时间：
2004-03-01
影响因子：
6
通讯作者：
Huard, J
中科院分区：
文献类型：
--
作者：
Li, Y;Foster, W;Huard, J
转化生长因子-β 1（TGF-β 1）被认为在纤维化疾病中起着至关重要的作用。本研究首次证明，TGF-β 1刺激可以诱导成肌细胞（C2 C12细胞）以自分泌方式表达TGF-β 1，下调生肌蛋白的表达，并启动体外纤维化相关蛋白的产生。将人重组TGF-β 1直接注射到体内骨骼肌中刺激肌原细胞（包括肌纤维）表达TGF-β 1，并诱导注射区域内的瘢痕组织形成。我们还观察到这种生长因子的局部表达的肌原细胞，包括再生肌纤维，在受伤的骨骼肌。最后，我们证明了TGF-β 1基因转染的成肌细胞（CT细胞）在肌内移植后可以分化成肌纤维母细胞，但核心蛋白聚糖，一种抗纤维化剂，通过阻断TGF-β 1阻止这种分化过程。总之，这些研究结果表明，TGF-β 1是一个主要的刺激剂，在骨骼肌纤维化级联的启动和诱导肌源性细胞分化为损伤肌肉中的肌纤维母细胞中起着重要作用。
Transforming growth factor-beta1 (TGF-beta1) is thought to play a crucial role in fibrotic diseases. This study demonstrates for the first time that TGF-beta1 stimulation can induce myoblasts (C2C12 cells) to express TGF-beta1 in an autocrine manner, down-regulate the expression of myogenic proteins, and initiate the production of fibrosis-related proteins in vitro. Direct injection of human recombinant TGF-beta1 into skeletal muscle in vivo stimulated myogenic cells, including myofibers, to express TGF-beta1 and induced scar tissue formation within the injected area. We also observed the local expression of this growth factor by myogenic cells, including regenerating myofibers, in injured skeletal muscle. Finally, we demonstrated that TGF-beta1 gene-transfected myoblasts (CT cells) can differentiate into myofibroblastic cells after intramuscular transplantation, but that decorin, an anti-fibrosis agent, prevents this differentiation process by blocking TGF-beta1. In summary, these findings indicate that TGF-beta1 is a major stimulator that plays a significant role in both the initiation of fibrotic cascades in skeletal muscle and the induction of myogenic cells to differentiate into myofibroblastic cells in injured muscle.