| The mdx mouse is the genetic homologue of Duchenne Muscular Dystrophy (DMD). In this model, repeated cycles of muscle fiber necrosis occur within the diaphragm and other muscles. It has been reported that molecules associated with tissue damage, such as extracellular matrix breakdown products, can act as endogenous ligands for Toll-Like receptors (TLRs). However, the role of TLRs and endogenous ligands released from damaged skeletal muscle has not been examined. The goals of this study were to determine whether genes associated with TLR function are abnormally regulated in mdx diaphragm and tibialis anterior and if TLR2 gene ablation affects genes associated with TLR signaling and inflammation. By quantitative RT-PCR, multiple genes associated with TLR signaling and inflammation were significantly upregulated in the mdx diaphragm and tibialis anterior muscles. Genetic ablation of TLR2 in mdx mice was associated with a significant downregulation of many pro-inflammatory genes. Our findings suggest that genes of the TLR signaling pathway are upregulated in mdx skeletal muscles and are linked to excessive inflammation. |
