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LIF is a contraction-induced myokine stimulating human myocyte proliferation.
- Source :
-
Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2011 Jul; Vol. 111 (1), pp. 251-9. Date of Electronic Publication: 2011 Apr 28. - Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- Adult
Biopsy
Cells, Cultured
Electric Stimulation
Humans
Leukemia Inhibitory Factor genetics
Male
Muscle Fibers, Skeletal drug effects
Phosphatidylinositol 3-Kinases metabolism
Phosphoinositide-3 Kinase Inhibitors
Phosphorylation
Protein Kinase Inhibitors pharmacology
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
Proto-Oncogene Proteins c-jun metabolism
Proto-Oncogene Proteins c-myc metabolism
Quadriceps Muscle drug effects
RNA Interference
RNA, Messenger metabolism
Receptors, OSM-LIF genetics
Receptors, OSM-LIF metabolism
Recombinant Proteins metabolism
TOR Serine-Threonine Kinases antagonists & inhibitors
TOR Serine-Threonine Kinases metabolism
Time Factors
Young Adult
Cell Communication drug effects
Cell Proliferation drug effects
Leukemia Inhibitory Factor metabolism
Muscle Contraction
Muscle Fibers, Skeletal metabolism
Quadriceps Muscle metabolism
Resistance Training
Satellite Cells, Skeletal Muscle metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1601
- Volume :
- 111
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of applied physiology (Bethesda, Md. : 1985)
- Publication Type :
- Academic Journal
- Accession number :
- 21527666
- Full Text :
- https://doi.org/10.1152/japplphysiol.01399.2010