Journal
GROWTH HORMONE & IGF RESEARCH
Volume 30-31, Issue -, Pages 1-10Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.ghir.2016.07.002
Keywords
IGFBP-2; Dystrophy; Muscle; Fiber type; Muscle function
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Funding
- Muscular Dystrophy Association, U.S.A.
- National Health & Medical Research Council of Australia (NHMRC)
- Operational Infrastructure Support Program of the Victorian Government
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Objective: The insulin-like growth factor binding proteins (IGFBPs) are thought to modulate cell size and homeostasis via IGF-I-dependent and-independent pathways. There is a considerable dearth of information regarding the function of IGFBPs in skeletal muscle, particularly their role in the pathophysiology of Duchenne muscular dystrophy (DMD). In this study we tested the hypothesis that intramuscular IGFBP-2 overexpression would ameliorate the pathology in mdx dystrophic mice. Design: 4 week old male C57BI/10 and mdx mice received a single intramuscular injection of AAV6-empty or AAV6-IGFBP-2 vector into the tibialis anterior muscle. At 8 weeks post-injection the effect of IGFBP-2 overexpression on the structure and function of the injected muscle was assessed. Results: AAV6-mediated IGFBP-2 overexpression in the tibialis anterior (TA) muscles of 4-week-old C57BL/10 and mdx mice reduced the mass of injected muscle after 8 weeks, inducing a slower muscle phenotype in C57BL/10 but not mdx mice. Analysis of inflammatory and fibrotic gene expression revealed no changes between control and IGFBP-2 injected muscles in dystrophic (mdx) mice. Conclusions: Together these results indicate that the IGFBP-2-induced promotion of a slower muscle phenotype is impaired in muscles of dystrophin-deficient mdx mice, which contributes to the inability of IGFBP-2 to ameliorate the dystrophic pathology. The findings implicate the dystrophin-glycoprotein complex (DGC) in the signaling required for this adaptation. (C) 2016 Elsevier Ltd. All rights reserved.
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