TY - JOUR

T1 - LIF is a contraction-induced myokine stimulating human myocyte proliferation

AU - Broholm, Christa

AU - Laye, Matthew J

AU - Brandt, Claus

AU - Vadalasetty, Radhika

AU - Pilegaard, Henriette

AU - Pedersen, Bente Klarlund

AU - Schéele, Camilla Charlotte

PY - 2011

Y1 - 2011

N2 - Background: The cytokine leukemia inhibitory factor (LIF) is expressed by skeletal muscle and induces proliferation of myoblasts. We hypothesized that LIF is a contraction-induced myokine functioning in an autocrine fashion to activate gene regulation of human muscle satellite cell proliferation. Methods: Skeletal muscle LIF expression, regulation and action were examined in two models: 1) Young men performing a bout of heavy resistance exercise of the quadriceps muscle and 2) cultured primary human satellite cells. Results: Resistance exercise induced a 9-fold increase in LIF mRNA content in skeletal muscle, but LIF was not detectable in plasma of the subjects. However, electrically stimulated cultured human myotubes produced and secreted LIF, suggesting that LIF is a myokine with local effects. The well-established exercise-induced signaling molecules PI3K, Akt and mTor contributed to the regulation of LIF in cultured human myotubes as chemical inhibition of PI3K and mTor and siRNA knockdown of Akt1 were independently sufficient to down regulate LIF. Human myoblast proliferation was increased by recombinant exogenous LIF and decreased by siRNA knockdown of the endogenous LIF receptor. Finally, the transcription factors JunB and c-Myc, which promote myoblast proliferation, were induced by LIF in cultured human myotubes. Indeed, both JunB and c-Myc were also increased in skeletal muscle following resistance exercise. Conclusion: Our data suggest that LIF is a contraction-induced myokine, potentially acting in an autocrine or paracrine fashion to promote satellite cell proliferation.

AB - Background: The cytokine leukemia inhibitory factor (LIF) is expressed by skeletal muscle and induces proliferation of myoblasts. We hypothesized that LIF is a contraction-induced myokine functioning in an autocrine fashion to activate gene regulation of human muscle satellite cell proliferation. Methods: Skeletal muscle LIF expression, regulation and action were examined in two models: 1) Young men performing a bout of heavy resistance exercise of the quadriceps muscle and 2) cultured primary human satellite cells. Results: Resistance exercise induced a 9-fold increase in LIF mRNA content in skeletal muscle, but LIF was not detectable in plasma of the subjects. However, electrically stimulated cultured human myotubes produced and secreted LIF, suggesting that LIF is a myokine with local effects. The well-established exercise-induced signaling molecules PI3K, Akt and mTor contributed to the regulation of LIF in cultured human myotubes as chemical inhibition of PI3K and mTor and siRNA knockdown of Akt1 were independently sufficient to down regulate LIF. Human myoblast proliferation was increased by recombinant exogenous LIF and decreased by siRNA knockdown of the endogenous LIF receptor. Finally, the transcription factors JunB and c-Myc, which promote myoblast proliferation, were induced by LIF in cultured human myotubes. Indeed, both JunB and c-Myc were also increased in skeletal muscle following resistance exercise. Conclusion: Our data suggest that LIF is a contraction-induced myokine, potentially acting in an autocrine or paracrine fashion to promote satellite cell proliferation.

U2 - 10.1152/japplphysiol.01399.2010

DO - 10.1152/japplphysiol.01399.2010

M3 - Journal article

C2 - 21527666

VL - 111

SP - 251

EP - 259

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 1

ER -