Skeletal muscle regeneration is attenuated with the repression of the cytoskeletal protein, Xin

Xin, an actin binding protein, has been implicated in the regulation of satellite cell function and is hypothesized to be essential for skeletal muscle regeneration following injury. Using Xin shRNA adenovirus (XinAd), endogenous Xin expression was reduced in regenerating skeletal muscles, isolated single myofibers and C2C12 myoblasts to investigate the role of Xin in the muscle repair process. Morphological analysis revealed significantly smaller fiber areas and more centrally located nuclei in Xin silenced muscle at 5 and 14 days of regeneration compared to control. Furthermore, Xin silenced muscle displayed elevated apoptosis relative to control infected muscle. Satellite cell activation and proliferation were both significantly decreased which, in addition to elevated apoptosis, could explain the delayed regeneration. Together, these data demonstrate the critical role for Xin in satellite cell regulation and, ultimately, skeletal muscle repair.