Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease for which there is no cure and limited treatment options. Prednisone is currently the first line treatment option for DMD and studies have demonstrated that prednisone improves muscle strength. Although prednisone has been used for the treatment of DMD for decades, the mechanism of action of this drug remains unclear. Recent studies have shown that the α7β1 integrin is a major modifier of disease progression in mouse models of DMD and therefore a target for drug-based therapies. In this study we examined if prednisone increased α7β1 integrin levels in mdx and GRMD models and myogenic cells from DMD patients. Our results showed prednisone promotes an increase in α7 integrin protein in cultured myogenic cells and in the muscle of mdx and GRMD animal models of DMD. The prednisone mediated increase in α7 integrin was associated with increased laminin-α2 in prednisone treated dystrophin-deficient muscle. Together our results suggest that prednisone acts in part through increased merosin in the muscle basal lamina and sarcolemmal stabilization of the α7β1 integrin in dystrophin-deficient muscle. These results indicate therapies that target an increase in muscle α7β1 integrin, its signaling pathways and/or laminin may be therapeutic in DMD.
- Received February 20, 2013.
- Accepted June 27, 2013.
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