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09-01-2012 | Physiology | Article

Srf protein pivotal to skeletal muscle growth


Free abstract

MedWire News: A protein producted in muscle fibers, serum response factor (Srf), has a newly identified role in promoting muscle growth, French researchers believe based on an animal study.

They report that Srf is pivotal in translating the mechanical signals from working muscle into chemical signals. "It is unexpected and quite interesting," said Athanassia Sotiropoulos (INSERM, Institut Cochin, Paris, France), the study's lead author, in an accompanying press statement.

Sotiropoulos and team probed the role of Srf, a ubiquitously expressed transcription factor that targets, among others, a muscle-specific set of genes encoding sarcomeric proteins.

Srf in muscle has recently been shown to become less prevalent with increasing age and there is accumulating evidence that Srf is involved in controlling skeletal muscle mass during hypertrophy.

To investigate further, Sotiropoulos et al used a mouse model of conditional and inducible loss of Srf within myofibers but not in satellite stem cells.

They found that Srf-deficient myofibers did not become hypertrophic when subjected to experimental overload. This suggests that Srf is required for the muscle growth response in response to increased activity, the researchers note.

They then used in vivo and in vitro assays to assess the underlying molecular mechanisms of this response. They found that the role of Srf in promoting hypertrophy was due to lack of satellite cell proliferation and fusion to pre-existing myofibers.

This is a new finding, say Sotiropoulos et al, who note that Srf was previously thought to work via the IGF1/Akt signaling pathway.

Finally, they identified a network of genes through which Srf works, which encompasses not only Srf but also the interleukin-6 (Il6), interleukin-4 (Il4), and cyclo-oxygenase-2 (Cox2) genes.

"By modulating Il6, Cox2, and Il4 expression levels in the myofibers, Srf controls both satellite stem cell proliferation and fusion," writes the team.

The involvement of Cox2 raises the intriguing possibility that Cox-2 inhibition with drugs such as ibuprofen could work against muscle growth and recovery, they note.

Furthermore, therapeutic manipulation of Il6, Cox2, or Il4 could potentially activate muscle stem cells and enhance muscle growth - an effect that could be valuable in old age or following prolonged immobility, they add.

The team concludes: "These findings unravel a role for Srf in the translation of mechanical cues applied to myofibers into paracrine signals, which in turn will modulate satellite cell functions and support muscle growth."

By Joanna Lyford

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