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Erythropoietin in myoblast maintenance and muscle regeneration
Author(s) -
Jia yi,
Suzuki Norio,
Yamamoto Masayuki,
Gassmann Max,
Noguchi Constance Tom
Publication year - 2008
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.22.2_supplement.581
Subject(s) - erythropoietin receptor , erythropoietin , myocyte , c2c12 , regeneration (biology) , myogenesis , microbiology and biotechnology , protein kinase b , biology , signal transduction , endocrinology , medicine , apoptosis , biochemistry
Preserving myoblast survival is essential in muscle regeneration. Erythropoietin (Epo), required for erythrocyte production, has been shown to stimulate proliferation and retard differentiation of cultured myoblasts. We find that endogenous Epo signaling and Epo treatment promote myoblasts survival and muscle regeneration. Epo protects C2C12 cultures from low oxygen induced apoptosis and activates the EpoR‐AKT signaling pathway. Epo promotes myoblasts growth after cell disruption in culture with optimal concentration of 5U/mL. Myoblasts cultures from Tg6 mice with over expression of Epo proliferate significantly faster compared to WT littermates, while the myoblasts from EpoR‐erythroid mice without EpoR in non‐hematopoietic tissue grow slower. Following cardiotoxin injection, healing Tg6 muscles contain more myoblasts and show increased muscle strength compared to WT littermates, while EpoR‐erythroid mice have fewer myoblasts and decreased muscle strength. Epo treatment further decreases wounded muscle fibers, increases myoblasts number and muscle strength in Tg6 mice and WT mice. In conclusion, endogenous Epo signaling protects myoblasts from apoptosis and facilitates wounded muscle regeneration that may be related to the EpoR‐AKT signaling pathway. This activity is independent of erythrocyte production, and can be augmented by exogenous Epo treatment.