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The exercise‐regulated myokine chitinase‐3‐like protein 1 stimulates human myocyte proliferation
Author(s) -
Görgens S. W.,
Hjorth M.,
Eckardt K.,
Wichert S.,
Norheim F.,
Holen T.,
Lee S.,
Langleite T.,
Birkeland K. I.,
Stadheim H. K.,
Kolnes K. J.,
Tangen D. S.,
Kolnes A. J.,
Jensen J.,
Drevon C. A.,
Eckel J.
Publication year - 2016
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12579
Subject(s) - myocyte , myogenesis , skeletal muscle , endocrinology , medicine , muscle hypertrophy , biology , microbiology and biotechnology , protein kinase b , signal transduction , chemistry
Aim Chitinase‐3‐like protein 1 ( CHI 3L1) is involved in tissue remodelling and inflammatory processes. Plasma levels are elevated in patients with insulin resistance and T2 DM . We recently showed that CHI 3L1 and its receptor protease‐activated receptor 2 ( PAR ‐2) are expressed in skeletal muscle. Activation of PAR ‐2 by CHI 3L1 protects against TNF ‐ α ‐induced inflammation and insulin resistance. However, the effect of exercise on CHI 3L1 and PAR ‐2 signalling remains unknown. The aim of this work was to study the impact of exercise on CHI 3L1 production and the effect of CHI 3L1/ PAR ‐2 signalling on skeletal muscle growth and repair. Methods Three human exercise studies were used to measure CHI 3L1 plasma levels ( n = 32). In addition, muscle and adipose tissue CHI 3L1 mRNA expression was measured in response to acute and long‐term exercise ( n = 24). Primary human skeletal muscle cells were differentiated in vitro, and electrical pulse stimulation was applied. In addition, myoblasts were incubated with CHI 3L1 protein and activation of MAP kinase signalling as well as proliferation was measured. Results Circulating CHI 3L1 levels and muscle CHI 3L1 mRNA were increased after acute exercise. In addition, CHI 3L1 mRNA expression as well as CHI 3L1 secretion was enhanced in electrically stimulated cultured myotubes. Incubation of cultured human myoblasts with CHI 3L1 protein leads to a strong activation of p44/42, p38 MAPK and Akt as well as enhanced myoblast proliferation. Conclusion Our findings suggest that CHI 3L1 is induced by acute exercise and that CHI 3L1/ PAR ‐2 signalling activates myocyte proliferation, which is important for restructuring of skeletal muscle in the response to exercise training.