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Purinoceptor expression in regenerating skeletal muscle in the mdx mouse model of muscular dystrophy and in satellite cell cultures
Author(s) -
Ryten Mina,
Yang Shi Yu,
Dunn Philip M.,
Goldspink Geoffrey,
Burnstock Geoffrey
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-1175fje
Subject(s) - purinergic receptor , myogenesis , skeletal muscle , microbiology and biotechnology , muscular dystrophy , biology , myocyte , regeneration (biology) , receptor , mdx mouse , itga7 , duchenne muscular dystrophy , purinergic signalling , colocalization , dystrophin , medicine , extracellular , endocrinology , biochemistry , adenosine receptor , genetics , agonist
ATP is an important extracellular signaling molecule mediating its effects by activation of P2X and P2Y receptors. P2 receptors are expressed during muscle development, and recent findings demonstrate that ATP can regulate myoblast proliferation and differentiation in vitro. However, the role of purinergic signaling during regeneration of injured skeletal muscle has not been investigated. To examine this process in a clinically relevant system, we used the mouse model of muscular dystrophy ( mdx ), in which muscle degeneration is rapidly followed by regeneration. The latter process, in vivo muscle regeneration, was the focus of this study, and to study the cellular mechanisms involved in it, a parallel study on normal rat skeletal myoblast cultures was conducted. Using immunohistochemistry, RT‐PCR, and electrophysiology, we investigated the expression of the P2X 1‐7 receptor subtypes and the P2Y 1,2,4,6 receptors. Experiments in vitro and in vivo demonstrated the sequential expression of the P2X 5 , P2Y 1 , and P2X 2 receptors during the process of muscle regeneration. The P2X 5 and P2Y 1 receptors were expressed first on activated satellite cells, and the P2Y 1 receptor was also expressed on infiltrating immune cells. Subsequent P2X 2 receptor expression on newly formed myotubes showed significant colocalization with AChRs, suggesting a role in regulation of muscle innervation. Thus, this study provides the first evidence for a role for purinergic signaling in muscle regeneration and raises the possibility of new therapeutic strategies in the treatment of muscle disease.