Fibroblast growth factor 2-stimulated proliferation is lower in muscle precursor cells from old rats

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Kevin Zwetsloot Ph.D, Associate Professor (Creator)
Appalachian State University (ASU )
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Abstract: In aged skeletal muscle, impairments in regrowth and regeneration may be explained by a decreased responsiveness of muscle precursor cells (MPCs) to environmental cues such as growth factors. We hypothesized that impaired responsiveness to fibroblast growth factor 2 (FGF2) in MPCs from old animals would be explained by impaired FGF2 signalling. We determined that 5-bromo-2f-deoxyuridine (BrdU) incorporation and cell number increase less in MPCs from 32- compared with 3-month-old rats. In the presence of FGF2, we demonstrated that there were age-associated differential expression patterns for FGF receptor 1 and 2 mRNAs. Measurement of downstream signalling revealed that that mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2)–extracellular signal-regulated kinase 1/2, protein kinase C and p38 were FGF2-driven pathways in MPCs. Uniquely, protein kinase C signalling was shown to play the largest role in FGF2-stimulated proliferation in MPCs. c-Jun N-terminal kinase (JNK) signalling was ruled out as an FGF2-stimulated proliferation pathway in MPCs. Inhibition of JNK had no effect on FGF2 signalling to BrdU incorporation, and FGF2 treatment was associated with increased phosphorylation of p38, which inhibits, rather than stimulates, BrdU incorporation in MPCs. Surprisingly, the commonly used vehicle, dimethyl sulphoxide, 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.

Additional Information

Seth S. Jump, Tom E. Childs, Kevin A. Zwetsloot, Frank W. Booth and Simon J. Lees (2009) "Fibroblast growth factor 2-stimulated proliferation is lower in muscle precursor cells from old rats" Experimental Physiology. 94(6). 739-748. Version of Record available @ (doi: 10.1113/expphysiol.2008.046136.)
Language: English
Date: 2009
fibroblast, growth-factor, proliferation, muscle-precursor-cells

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