Mutations in the Lmod3 gene have been identified as a genetic cause of nemaline myopathy. However, the mechanism underlying this disease and the function of Lmod3 remain largely unknown. In this study, we found that Lmod3 knockdown in C2C12 cells impaired myoblast differentiation, whereas enforced Lmod3 expression enhanced such differentiation. We also discovered that myoblast proliferation was promoted by Lmod3 overexpression but impeded by its knockdown. Additionally, knockdown of Lmod3 led to apoptosis in myoblasts. Concurrently, forced Lmod3 expression in C2C12 cells contributed to activation of the AKT and ERK pathways during myoblast differentiation and proliferation, respectively. Conversely, knockdown of Lmod3 in C2C12 cells produced the opposite results. Furthermore, administration of IGF-1, a booster of both AKT and ERK pathways, partially rescued the inhibitory effect of Lmod3 knockdown on both differentiation and proliferation of C2C12 cells. These results suggest that Lmod3 promotes differentiation and proliferation of myoblasts through the AKT and ERK pathways, respectively.

Lmod3基因中的突变已被确定为肾形肌病的遗传原因。但是，这种疾病的潜在机制和Lmod3的功能仍然未知。在这项研究中，我们发现C2C12细胞中的Lmod3敲低损害成肌细胞的分化，而增强的Lmod3表达则增强了这种分化。我们还发现成肌细胞增殖是由Lmod3过表达促进的，但其敲低会阻碍成肌的增殖。另外，Lmod3的敲低导致成肌细胞凋亡。同时，强制使用Lmod3在成肌细胞分化和增殖过程中，C2C12细胞中的表达分别促进了AKT和ERK通路的激活。相反，在C2C12细胞中敲低Lmod3产生相反的结果。此外，IGF-1（AKT和ERK途径的增强剂）的施用部分挽救了Lmod3敲低对C2C12细胞分化和增殖的抑制作用。这些结果表明，Lmod3分别通过AKT和ERK途径促进成肌细胞的分化和增殖。