Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK/ERK signaling pathway

Abstract

Sarcopenia is the age-related loss of muscle and fiber number and decreased regenerative capacity with increased abundance of reactive oxygen species levels and electron transport chain abnormalities. The aim of this study was to investigate the antisarcopenia effect of MFG-E8 in alleviating skeletal muscle dysfunction induced by D-galactose, and reveal the mechanism promoting myoblast cell proliferation and mediating the cell cycle. This in vivo experiment showed that MFG-E8 can improve the antioxidant status and increase soleus muscle mass (35.61%) and fiber diameter (39.72%) in the aging rats. The western blot assay preliminarily proved that increased ERK phosphorylation determines the repairment of injured skeletal muscle, but not JNK and p38. In vitro experiments further verified that MFG-E8 can increase the number of mitochondria, cell vitality, cell density, and reduce apoptosis rate. Flow cytometry and quantitative real-time PCR proved that MFG-E8 promoted cell proliferation by upregulating mRNA expression of cyclin D1, cyclin E1, CDK, and downregulating mRNA expression of p21 and p27, thereby increasing the S and G₂/M phase and decreasing the G₀/G₁ phase. Molecular level further proved that MFG-E8 mediated cell cycle and promoted cell proliferation by activating the MAPK/ERK signaling pathway.