Lithium Chloride Preconditioning Optimizes Skeletal Myoblast Functions for Cellular Cardiomyoplasty in vitro via Glycogen Synthase Kinase-3β/β-Catenin Signaling

The benefits of skeletal myoblast (SkM) transplantation for cardiomyoplasty are limited due to their decreased functional integration with host cardiomyocytes and the poor survival of implanted cells in ischemic hearts. However, little success has been achieved with respect to the strategies aiming to improve the efficiency of SkM transplantation. In this study, we demonstrated that LiCl-preconditioned SkMs resulted in significantly increased connexin 43 (Cx43) expression and gap-junctional communication with cardiomyocytes. Vascular endothelial growth factor (VEGF) expression of SkMs was significantly upregulated in response to LiCl. Furthermore, hydrogen peroxide induced SkM apoptosis and increased caspase-3 expression, whereas LiCl inhibited SkM apoptosis, resulted in the decrease of caspase-3 expression and promoted SkM proliferation. These effects of LiCl were mediated by inactivating glycogen synthase kinase-3beta (GSK-3beta), stabilizing the effector protein beta-catenin and translocating it into the nucleus of SkMs, confirming that LiCl mimics canonical Wnt signaling. These findings suggest that LiCl preconditioning may be a novel strategy to optimize SkM function for cellular cardiomyoplasty in vitro.