LIF is a contraction-induced myokine stimulating human myocyte proliferation

被引:116
作者
Broholm, Christa [1 ]
Laye, Matthew J. [1 ]
Brandt, Claus [1 ]
Vadalasetty, Radhika [1 ]
Pilegaard, Henriette [2 ]
Pedersen, Bente Klarlund [1 ]
Scheele, Camilla [1 ]
机构
[1] Univ Copenhagen, CIM, Rigshosp, Dept Infect Dis,Fac Hlth Sci, DK-2100 Copenhagen, Denmark
[2] Univ Copenhagen, CIM, Dept Biol, DK-2100 Copenhagen, Denmark
基金
新加坡国家研究基金会;
关键词
skeletal muscle; satellite cells; resistance exercise; leukemia inhibitory factor; LEUKEMIA INHIBITORY FACTOR; SKELETAL-MUSCLE HYPERTROPHY; RESISTANCE EXERCISE; GENE-EXPRESSION; MYOGENIC DIFFERENTIATION; PROTEIN-SYNTHESIS; GROWTH-FACTOR; INTERLEUKIN-6; CELLS; MTOR;
D O I
10.1152/japplphysiol.01399.2010
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Broholm C, Laye MJ, Brandt C, Vadalasetty R, Pilegaard H, Pedersen BK, Scheele C. LIF is a contraction- induced myokine stimulating human myocyte proliferation. J Appl Physiol 111: 251-259, 2011. First published April 28, 2011; doi:10.1152/japplphysiol.01399.2010.-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. 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. Resistance exercise induced a ninefold 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 downregulate 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. Our data suggest that LIF is a contraction- induced myokine, potentially acting in an autocrine or paracrine fashion to promote satellite cell proliferation.
引用
收藏
页码:251 / 259
页数:9
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