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

Abstract

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. To investigate the role of Xin during skeletal muscle regeneration, we inhibited Xin expression using a Xin shRNA adenoviral (XinAd) injection into the right tibialis anterior (TA) of 6 week old male mice, while the left TA served as a control receiving an injection of the virus lacking Xin shRNA. Injury was induced in both TAs 4 days later via cardiotoxin injection. At 5 days post‐injury, muscle fiber area was significantly smaller (Control: 1007 ± 62 μm2 ; Xin Ad: 785± 73 μm2) and the number of centrally located nuclei per muscle fiber was significantly increased (134 ± 9%) in XinAd regenerating muscle compared to control. These deficits in fiber area (Control: 3136±278 μm2;Xin Ad: 2273 ±167 μm2) and centrally located nuclei (137 ± 9% of control) in the XinAd muscles persisted to 14 days regeneration suggesting that the regenerating muscle injected with XinAd is less mature at 5 and 14 days of regeneration. A significant increase in apoptosis (TUNEL) at 5 and 14 days of regeneration (126±6%; 141±12% of control) was observed in the XinAd TA compared to control. These data support the hypothesis that Xin is important for muscle regeneration and future work will investigate the roles of Xin on satellite cell activation and maturation.