Protease-activated receptor-2 mediates proliferative responses in skeletal myoblasts.
Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved by proteases within the N terminus, exposing a new tethered ligand that binds and activates the receptor. Activators of PAR-2 include trypsin and mast cell tryptase. Skeletal myoblasts are known to express PAR-1, a thrombin receptor. The current study was undertaken to determine whether myoblasts express PAR-2. Primary neonatal rat and mouse skeletal myoblast cultures were shown to express PAR-2 in polymerase chain reaction and immunocytochemical studies. Expression of PAR-2 was also demonstrated by immunohistochemistry in developing mouse skeletal muscle in vivo. Trypsin or a synthetic peptide corresponding to the rat PAR-2 tethered ligand caused a dose-dependent elevation in intracellular calcium in cultured rat myoblasts, with an EC(50) of 13 nM or 56 microM, respectively. Studies aimed at identifying the function of PAR-2 in myoblasts demonstrated no effect of the receptor-activating peptide on survival or fusion in serum-deprived myoblasts. The PAR-2-activating peptide did, however, stimulate proliferation of serum-deprived myoblasts. These results demonstrate that skeletal muscle cells express PAR-2, activation of which leads to stimulation of myoblast proliferation.
Chinni
C
C
School of Veterinary Science, University of Melbourne, Parkville, Victoria 3010, Australia.
de Niese
M R
MR
Jenkins
A L
AL
Pike
R N
RN
Bottomley
S P
SP
Mackie
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002459:Cell Fusion; D002478:Cells, Cultured; D015870:Gene Expression; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology*; D051381:Rats; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*
D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D002118:Calcium