Renalase knockdown inhibits proliferation of mouse satellite cells

Skeletal muscle regeneration is mediated by skeletal muscle stem cells, known as satellite cells. Satellite cell proliferation is regulated by various secreted factors, including exercise-induced cytokines. Renalase is a protein that promotes cell proliferation through activation of intracellular signaling pathways in tumor cells. However, the role of renalase in satellite cell proliferation remains unclear. This study aimed to elucidate the role of renalase in satellite cell proliferation. Satellite cells were isolated from the extensor digitorum longus (EDL) muscles of male mice. Renalase expression was suppressed using an adenoviral vector expressing short hairpin RNA (shRNA). Renalase knockdown significantly suppressed cell numbers, particularly reducing the Pax7⁺/MyoD⁺ cell population. In addition, the numbers of Ki67-positive and EdU-positive cells were significantly reduced, and the expression of genes involved in cell-cycle progression was significantly decreased. Furthermore, the phosphorylation levels of ERK1/2 and Akt, key signaling molecules involved in cell proliferation, were significantly reduced following renalase knockdown. These results indicate that renalase is essential for satellite cell proliferation and that renalase knockdown inhibits satellite cell proliferation by suppressing the Akt–mTOR and ERK1/2 signaling pathways.