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Am J Physiol Cell Physiol (March 6, 2002). doi:10.1152/ajpcell.00574.2001
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Articles in PresS, published online ahead of print March 6, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00574.2001
Submitted on December 4, 2001
Accepted on February 28, 2002

Multiple Signaling Pathways Mediate LIF-Induced Skeletal Muscle Satellite Cell Proliferation

Espen E Spangenburg1 and Frank W Booth1*

1 Veterinary Biomedical Sciences, University of Missouri-Columbia, Columbia, MO, USA

* To whom correspondence should be addressed. E-mail: boothf{at}missouri.edu, pellg@missouri.edu.

There are many known growth factors/cytokines that induce skeletal muscle satellite cell proliferation. Currently, the signaling mechanisms in which these growth factors/cytokines activate satellite cell proliferation are not completely understood. Here, we sought to determine signaling mechanisms by which Leukemia Inhibitory Factor (LIF) induces satellite cell proliferation in culture. First, we confirm that LIF induces proliferation of C2C12 immortalized myoblasts and cultured primary rat satellite cells. In addition, we also found that this increase in proliferation can be inhibited by incubation of the cells in AG490, a specific inhibitor of JAK2 activity. Further, we also find that incubation of the cells at various time points with LIF (10ng/ml) induces a significant transient increase in JAK2 phosphorylation, STAT3 phosphorylation, and STAT3 transcriptional activity. Increases in the STAT3-sensitive endogenous SOC3 protein followed these transient increases in STAT3 activation. In addition, AG490 inhibited the increase in STAT3 phosphorylation. Finally, LIF did not change the phosphorylation status of ERK1/2 or affect the phosphorylation status of AKT/PKB. However, LY294002, an inhibitor of PI3K, blocked LIF-induced proliferation of satellite cells. These data suggest that LIF induces satellite cell proliferation by activation of the JAK2-STAT3 signaling pathway, suggesting that this may be an important pathway in muscle growth and/or hypertrophy.




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