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Myogenin regulates denervation‐dependent muscle atrophy in mouse soleus muscle
Author(s) -
Macpherson Peter C. D.,
Wang Xun,
Goldman Daniel
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23136
Subject(s) - denervation , myogenin , soleus muscle , atrophy , muscle atrophy , amyotrophy , medicine , endocrinology , chemistry , anatomy , myocyte , biology , skeletal muscle , myogenesis
Muscle inactivity due to injury or disease results in muscle atrophy. The molecular mechanisms contributing to muscle atrophy are poorly understood. However, it is clear that expression of atrophy‐related genes, like Atrogin‐1 and MuRF‐1, are intimately tied to loss of muscle mass. When these atrophy‐related genes are knocked out, inactive muscles retain mass. Muscle denervation stimulates muscle atrophy and Myogenin (Myog) is a muscle‐specific transcription factor that is highly induced following muscle denervation. To investigate if Myog contributes to muscle atrophy, we have taken advantage of conditional Myog null mice. We show that in the denervated soleus muscle Myog expression contributes to reduced muscle force, mass, and cross‐sectional area. We found that Myog mediates these effects, at least in part, by regulating expression of the Atrogin‐1 and MuRF‐1 genes. Indeed Myog over‐expression in innervated muscle stimulates Atrogin‐1 gene expression and Myog over‐expression stimulates Atrogin‐1 promoter activity. Thus, Myog and the signaling cascades regulating its induction following muscle denervation may represent novel targets for therapies aimed at reducing denervation‐induced muscle atrophy. J. Cell. Biochem. 112: 2149–2159, 2011. © 2011 Wiley‐Liss, Inc.