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Akirin‐1 expression blocks dexmethosone induced satellite cell dysfunction
Author(s) -
Dong Yanjun,
Pan Jenny,
Dong Yanlan,
Mitch William E,
Zhang Liping
Publication year - 2013
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/fasebj.27.1_supplement.940.12
Subject(s) - myostatin , myod , myogenin , cell growth , muscle atrophy , biology , endocrinology , medicine , gene silencing , cell , downregulation and upregulation , satellite , microbiology and biotechnology , muscle hypertrophy , myocyte , skeletal muscle , myogenesis , gene , aerospace engineering , biochemistry , genetics , engineering
Glucocorticoids are elevated in many pathological conditions and are associated with muscle loss, but the mechanisms are not fully understood. Defects in satellite cell function contribute to the development of muscle atrophy. Here, we demonstrated a new mechanism of dexamethasone‐induced muscle atrophy by suppression of satellite cell function. Dexamethasone decreased satellite cell proliferation and differentiation in vitro and in vivo . This was associated with upregulation of myostatin and suppression of Akirin1, a promyogenic gene. Myostatin inhibition in dexamethasone‐treated mice increased Akirin1 expression, satellite cell activity, muscle regeneration and muscle growth. Silencing myostatin in satellite cells prevented dexamethasone suppression of Akirin1 expression and satellite cells proliferation and differentiation. Finally, overexpression of Akirin1 in satellite cells increased the expression of MyoD and myogenin and improved cell proliferation and differentiation even in the presence of dexamethasone. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression causing satellite cell dysfunction and muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could be therapeutic strategies to improve satellite cell activation and enhance muscle growth in diseases associated with increased glucocorticoid production.