Erythropoietin, the cytokine required for erythrocyte production, contributes to muscle progenitor cell proliferation and survival in culture and animal models. Erythropoietin induces transcription factors GATA-4 and TAL1 expression in myoblasts and knock down of GATA-4 or TAL1 changes myogenic regulatory factor expression program and promotes the myogenic differentiation. Sirtuin 1 activity, a NAD+ dependent deacetylation enzyme, myoblast cellular NAD+ level and NAD+/NADH ratio are increased by erythropoietin stimulation of C2C12 myoblasts. Sirtuin 1 knock down reduced GATA-4 and TAL1 expression and impaired the erythropoietin response suggesting that erythropoietin activity in myoblasts is mediated through GATA-4, TAL1 and Sirtuin 1. GATA-4 targets Sirtuin 1 to the myogenin promoter while TAL1 represses MyoD binding to and activation of the myogenin promoter. These data suggest a new pathway of erythropoietin activity in skeletal myoblasts affecting myogenic differentiation through cross-talk among Sirtuin1, GATA-4 and TAL1.

Project Start
Project End
Budget Start
Budget End
Support Year
37
Fiscal Year
2012
Total Cost
$362,920
Indirect Cost
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Dey, Soumyadeep; Noguchi, Constance T (2017) Erythropoietin and Hypothalamic-Pituitary Axis. Vitam Horm 105:101-120
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