Enhancing Muscle Membrane Repair by Gene Delivery of MG53 Ameliorates Muscular Dystrophy and Heart Failure in δ-Sarcoglycan-deficient Hamsters

• DOI: 10.1038/mt.2012.5
• Publication Date: 2012-02-07T13:36:40Z
• Authors: Bo He; Ru-hang Tang; Noah Weisleder; Bin Xiao; Zhenhua Yuan; Chuanxi Cai; Hua Zhu; Peihui Lin; Chunping Qiao; Jianbin Li; Christina Mayer; Juan Li; Jianjie Ma; Xiao Xiao
• Keywords: Dysferlin

Muscular dystrophies (MDs) are caused by genetic mutations in over 30 different genes, many of which encode for proteins essential the integrity muscle cell structure and membrane. Their deficiencies cause vulnerable to mechanical biochemical damages, leading membrane leakage, dystrophic pathology, eventual loss cells. Recent studies report that MG53, a muscle-specific TRIM-family protein, plays an role sarcolemmal repair. Here, we show systemic delivery overexpression human MG53 gene recombinant adeno-associated virus (AAV) vectors enhanced repair, ameliorated improved heart functions δ-sarcoglycan (δ-SG)-deficient TO-2 hamsters, animal model MD congestive failure. In addition, increased dysferlin level facilitated its trafficking through participation caveolin-3. also protected cells activating survival kinases, such as Akt, extracellular signal-regulated kinases (ERK1/2), glycogen synthase kinase-3β (GSK-3β) inhibiting proapoptotic protein Bax. Our results suggest enhancing repair machinery could be novel therapeutic approach cardiomyopathy, demonstrated here limb girdle (LGMD) 2F model.