Erythropoietin acts by binding to its cell surface receptor on erythroid progenitor cells to stimulate erythrocyte production. However, erythropoietin receptor expression extends beyond hematopoietic tissue including muscle progenitor/precursor cells. Mice with erythropoietin receptor restricted to hematopoietic tissue were used to assess contributions of endogenous erythropoietin to promote skeletal myoblast proliferation and survival, and wound healing in a mouse model of cardiotoxin induced muscle injury. Compared with wild type controls, these mice had fewer skeletal muscle satellite/progenitor cells and myoblasts that do not proliferate in culture, were more susceptible to skeletal muscle injury and showed decreased muscle tension to tear. In contrast, mice with chronic elevated circulating erythropoietin had more satellite cells and myoblasts with increased proliferation and survival in culture, decreased muscle injury and accelerated muscle recovery in tension to rupture. Skeletal muscle myoblasts also produced endogenous erythropoietin that increased at low oxygen tension. Erythropoietin promoted proliferation, survival and wound recovery in myoblasts via the phosphoinositide 3-kinase/AKT pathway. Therefore, endogenous and exogenous erythropoietin contribute to increasing satellite cell number following muscle injury, improve myoblast proliferation and survival, and promote repair and regeneration in this mouse induced muscle injury model independent of its effect on erythrocyte production.
|Piknova, Barbora; Park, Ji Won; Swanson, Kathryn M et al. (2015) Skeletal muscle as an endogenous nitrate reservoir. Nitric Oxide 47:10-16|
|Wang, Li; Di, Lijun; Noguchi, Constance Tom (2014) Erythropoietin, a novel versatile player regulating energy metabolism beyond the erythroid system. Int J Biol Sci 10:921-39|
|Wang, Li; Jia, Yi; Rogers, Heather et al. (2013) Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1? and AMPK activation. Int J Biochem Cell Biol 45:1155-64|
|Jia, Yi; Suzuki, Norio; Yamamoto, Masayuki et al. (2012) Endogenous erythropoietin signaling facilitates skeletal muscle repair and recovery following pharmacologically induced damage. FASEB J 26:2847-58|
|Teng, Ruifeng; Calvert, John W; Sibmooh, Nathawut et al. (2011) Acute erythropoietin cardioprotection is mediated by endothelial response. Basic Res Cardiol 106:343-54|
|Beleslin-?oki?, Bojana B; Coki?, Vladan P; Wang, Li et al. (2011) Erythropoietin and hypoxia increase erythropoietin receptor and nitric oxide levels in lung microvascular endothelial cells. Cytokine 54:129-35|
|Jia, Yi; Warin, Renaud; Yu, Xiaobing et al. (2009) Erythropoietin signaling promotes transplanted progenitor cell survival. FASEB J 23:3089-99|