Wnt5a/Ca2+/CaN/NFAT信号通路在成肌分化过程中的作用及其机制研究

骨骼肌损伤十分常见，治疗困难且易复发，甚至影响运动员的运动生涯。骨骼肌损伤后，成肌细胞在成肌因子调控下形成再生的肌纤维。但目前对于调控成肌分化的机制尚无定论，对于该问题的认识还远远不够，因此尽快阐明成肌细胞分化的调控机理，为骨骼肌损伤寻求更为理想的治疗措施成为亟待解决的重要课题。Wnt信号通路在骨骼肌发育分化和再生过程中是不可或缺的，那么Wnt/ca2+/CaN/NFAT通路在成肌分化中是否起到举足轻重的作用呢？其分子机制又是什么呢？鉴于此，本项目拟首先观察成肌分化过程中Wnt5a的表达，然后分别干预Wnt5a和TRPC3在成肌细胞中的表达来探讨它们在成肌分化中的作用，最后观察Wnt5a基因敲除小鼠骨骼肌发育分化的情况和干预成肌细胞Wnt5a的表达来阐明Wnt5a/Ca2+/CaN/NFAT通路在成肌分化中的作用及其机制，以期为肌肉损伤及肌再生障碍疾病的治疗提供新的干预靶点。

Skeletal muscle injuries are common in sports. Muscle injuries are intractable, have high rates and negative influnces on the sport careers of athletes. With the regulation, myogenic factors in the injured muscle regenerate the new myofibers. At present, there is no clear mechanism of the regulation of the myogenic differentiation and an effective treatment for the injured muscle needs to find. Wnt signaling pathway plays a vital role in the development and regeneration of skeletal muscle. Does Wnt5a/Ca2+/CaN/NFAT signaling play an important role on the myogenic differentiation? What is its mechanism? In view of this, the research wants to firstly investigate the Wnt5a expression in the myogenic differentiation, and then investigate the affection of Wnt5a and TRPC3 on the myogenic differentiation of C2C12 cells with the interference which is used to inhibit or overexpress their expression, finally observe the development of skeletal muscle in the mice which is knocked down with Wnt5a gene and discuss the effection of Wnt5a/Ca2+/CaN/NFAT signaling pathway on the myogenic differentiation and its mechanism with the interference with the expression of Wnt5a gene. This research wants to provide the new therapeutic target for the treatment of sports injury and disorders of muscular dysgenesis.