title: The exercise-regulated myokine chitinase-3-like protein 1 stimulates human myocyte proliferation.
abstract: OBJECTIVE
  Chitinase-3-like protein 1 (CHI3L1) is involved in tissue remodelling and inflammatory processes. Plasma levels are elevated in patients with insulin resistance and T2DM. We recently showed that CHI3L1 and its receptor protease-activated receptor 2 (PAR-2) are expressed in skeletal muscle. Activation of PAR-2 by CHI3L1 protects against TNF-α-induced inflammation and insulin resistance. However, the effect of exercise on CHI3L1 and PAR-2 signalling remains unknown. The aim of this work was to study the impact of exercise on CHI3L1 production and the effect of CHI3L1/PAR-2 signalling on skeletal muscle growth and repair.
  
  
  METHODS
  Three human exercise studies were used to measure CHI3L1 plasma levels (n = 32). In addition, muscle and adipose tissue CHI3L1 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 CHI3L1 protein and activation of MAP kinase signalling as well as proliferation was measured.
  
  
  RESULTS
  Circulating CHI3L1 levels and muscle CHI3L1 mRNA were increased after acute exercise. In addition, CHI3L1 mRNA expression as well as CHI3L1 secretion was enhanced in electrically stimulated cultured myotubes. Incubation of cultured human myoblasts with CHI3L1 protein leads to a strong activation of p44/42, p38 MAPK and Akt as well as enhanced myoblast proliferation.
  
  
  CONCLUSIONS
  Our findings suggest that CHI3L1 is induced by acute exercise and that CHI3L1/PAR-2 signalling activates myocyte proliferation, which is important for restructuring of skeletal muscle in the response to exercise training.
authors: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center (DDZ), Düsseldorf, Germany.
authors: S W
authors: SW
authors: Görgens
authors: Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: M
authors: M
authors: Hjorth
authors: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center (DDZ), Düsseldorf, Germany.|Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: K
authors: K
authors: Eckardt
authors: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center (DDZ), Düsseldorf, Germany.
authors: S
authors: S
authors: Wichert
authors: Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: F
authors: F
authors: Norheim
authors: Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: T
authors: T
authors: Holen
authors: Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: S
authors: S
authors: Lee
authors: Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: T
authors: T
authors: Langleite
authors: Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: K I
authors: KI
authors: Birkeland
authors: Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway.
authors: H K
authors: HK
authors: Stadheim
authors: Charles University Third Faculty of Medicine, Prague, Czech Republic.
authors: K J
authors: KJ
authors: Kolnes
authors: Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway.
authors: D S
authors: DS
authors: Tangen
authors: Charles University Third Faculty of Medicine, Prague, Czech Republic.
authors: A J
authors: AJ
authors: Kolnes
authors: Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway.
authors: J
authors: J
authors: Jensen
authors: Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: C A
authors: CA
authors: Drevon
authors: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center (DDZ), Düsseldorf, Germany.|German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.
authors: J
authors: J
authors: Eckel
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000502:physiology*; D000071451:Chitinase-3-Like Protein 1 / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D012333:RNA, Messenger
keywords: chitinase-3-like protein 1; exercise; skeletal muscle