Erythropoietin expression and myoblasts survival

Abstract

Erythropoietin (Epo) is mainly produced in the kidney and regulates erythroid differentiation. We previously reported that myoblasts express Epo receptor (EpoR) and Epo increases their proliferation. Myoblast isolated from transgenic mice (Tg6) overexpressing a human Epo transgene showed increased proliferation and reduced apoptosis at 5% O2 compared with WT myoblasts, due partly to Epo transgene expression in myoblasts. Epo treatment further increased proliferation and protection from apoptosis. Murine Epo (mEpo) mRNA expression was also higher in Tg6 myoblasts, suggesting that Epo may further induce Epo expression in myoblasts. Epo treatment increased mEpo mRNA in both Tg6 and WT myoblasts to a similar level. Reduced O2 further increased mEpo mRNA but not greater than Epo treatment alone, suggesting that mEpo was maximally expressed with Epo treatment. Although EpoR expression decreased with myoblast differentiation, mEpo mRNA remained unchanged. Similarly, mEpo mRNA expressed in the gastrocnemius muscles in vivo was higher level in Tg6 mice and mEpo mRNA in muscle increased after mice muscle injury in both Tg6 and WT mice. These results suggest that Epo signaling from endogenous Epo production in muscle from myoblasts and/or mature muscle fibers can promote myoblasts proliferation and survival and that Epo production in muscle can be further induced by exogenous Epo.