Research Center on Aging, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Am J Physiol Cell Physiol. 2010 Nov;299(5):C939-47. doi: 10.1152/ajpcell.00253.2010. Epub 2010 Sep 1.
Previous work has pointed to a role for the Wnt canonical pathway in fibrosis formation in aged skeletal muscles. In the present study, we studied the dystrophic mdx mouse, which displays skeletal muscle fibrosis. Our results indicated that the muscle resident stromal cell (mrSC) population in the muscles of dystrophic mice is higher than in the muscles of age-matched wild-type mice. Wnt3a promoted the proliferation of and collagen expression by cultured mrSCs but arrested the growth of and collagen expression by cultured myoblasts. Injections of Wnt3A in the tibialis anterior muscles of adult wild-type mice significantly enhanced the mrSC population and collagen deposition compared with the contralateral muscles. Conversely, an injection of the Wnt antagonist Dickkof protein (DKK1) into the skeletal muscles of mdx mice significantly reduced collagen deposition. These results suggested that the Wnt canonical pathway expands the population of mrSCs and stimulates their production of collagen as observed during aging and in various myopathies.
先前的研究表明 Wnt 经典途径在衰老骨骼肌纤维化形成中发挥作用。在本研究中，我们研究了表现出骨骼肌纤维化的 DMD 模型（mdx）小鼠。我们的结果表明，与年龄匹配的野生型小鼠相比，在 DMD 模型的肌肉中，肌肉驻留基质细胞（mrSC）群体更高。Wnt3a 促进培养的 mrSC 的增殖和胶原蛋白表达，但抑制培养的成肌细胞的生长和胶原蛋白表达。与对侧肌肉相比，在成年野生型小鼠的比目鱼肌中注射 Wnt3A 可显著增加 mrSC 群体和胶原蛋白沉积。相反，向 mdx 小鼠的骨骼肌注射 Wnt 拮抗剂 Dickkof 蛋白（DKK1）可显著减少胶原蛋白沉积。这些结果表明，Wnt 经典途径可扩增 mrSC 群体并刺激其产生胶原蛋白，如在衰老和各种肌病中观察到的那样。
