Cisternas Pedro, Henriquez Juan P, Brandan Enrique, Inestrosa Nibaldo C
Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, P.O. Box 114-D, Santiago, Chile.
Mol Neurobiol. 2014 Feb;49(1):574-89. doi: 10.1007/s12035-013-8540-5. Epub 2013 Sep 7.
The signaling pathways activated by Wnt ligands are related to a wide range of critical cell functions, such as cell division, migration, and synaptogenesis. Here, we summarize compelling evidence on the role of Wnt signaling on several features of skeletal muscle physiology. We briefly review the role of Wnt pathways on the formation of muscle fibers during prenatal and postnatal myogenesis, highlighting its role on the activation of stem cells of the adult muscles. We also discuss how Wnt signaling regulates the precise formation of neuromuscular synapses, by modulating the differentiation of presynaptic and postsynaptic components, particularly regarding the clustering of acetylcholine receptors on the muscle membrane. In addition, based on previous evidence showing that Wnt pathways are linked to several diseases, such as Alzheimer's and cancer, we address recent studies indicating that Wnt signaling plays a key role in skeletal muscle fibrosis, a disease characterized by an increase in the extracellular matrix components leading to failure in muscle regeneration, tissue disorganization and loss of muscle activity. In this context, we also discuss the possible cross-talk between the Wnt/β-catenin pathway with two other critical profibrotic pathways, transforming growth factor β and connective tissue growth factor, which are potent stimulators of the accumulation of connective tissue, an effect characteristic of the fibrotic condition. As it has emerged in other pathological conditions, we suggests that muscle fibrosis may be a consequence of alterations of Wnt signaling activity.
Wnt配体激活的信号通路与多种关键细胞功能相关，如细胞分裂、迁移和突触形成。在此，我们总结了关于Wnt信号在骨骼肌生理学若干特征中作用的有力证据。我们简要回顾了Wnt通路在产前和产后肌生成过程中对肌纤维形成的作用，强调其在激活成年肌肉干细胞中的作用。我们还讨论了Wnt信号如何通过调节突触前和突触后成分的分化来调控神经肌肉突触的精确形成，特别是关于肌肉膜上乙酰胆碱受体的聚集。此外，基于先前表明Wnt通路与多种疾病（如阿尔茨海默病和癌症）相关的证据，我们探讨了近期研究，这些研究表明Wnt信号在骨骼肌纤维化中起关键作用，骨骼肌纤维化是一种以细胞外基质成分增加为特征的疾病，导致肌肉再生失败、组织紊乱和肌肉活动丧失。在此背景下，我们还讨论了Wnt/β-连环蛋白通路与另外两条关键的促纤维化通路（转化生长因子β和结缔组织生长因子）之间可能存在的相互作用，这两条通路是结缔组织积累的有效刺激因子，是纤维化状态的一个特征性效应。正如在其他病理状况中所显现的那样，我们认为肌肉纤维化可能是Wnt信号活性改变的结果。
