Fgf2-stimulated proliferation is lower in muscle precursor cells from old rats
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] In aged skeletal muscle, impairments in the regrowth and regeneration may be explained by a decreased responsiveness of muscle precursor cells (MPCs), or satellite cells, to environmental cues such as growth factors. We determined that in the presence of FGF2, BrdU incorporation and cell number increase less in MPCs from 32-mo old, compared to 3-mo-old animals. In the presence of FGF2, we demonstrated that there were age-associated differential expression patterns for FGFR1 and FGFR2 mRNAs. Measurement of downstream signaling revealed that MEK 1/2-ERK 1/2, PKC, and p38 were FGF2-driven pathways in MPCs. Uniquely, PKC signaling was shown to play the largest role in FGF2-stimulated proliferation in MPCs. Inhibition of JNK had no effect on FGF2 signaling to BrdU incorporation, while FGF2 treatment was associated with increased phosphorylation of p38, which inhibits, rather than stimulates, BrdU incorporation in MPCs. Unexpectedly, the commonly used vehicle, DMSO, rescued proliferation in MPCs from old animals. These findings provide insight for the development of effective treatment strategies that target the age-related impairments of MPC proliferation in old skeletal muscle.
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