Matrix metalloproteinases are involved in mechanical stretch-induced activation of skeletal muscle satellite cells.
When skeletal muscle is stretched or injured, myogenic satellite cells are activated to enter the cell cycle. This process depends on nitric oxide (NO) production, release of hepatocyte growth factor (HGF) from the extracellular matrix, and presentation of HGF to the c-met receptor. Experiments reported herein provide new evidence that matrix metalloproteinases (MMPs) are involved in the NO-dependent release of HGF in vitro. When rat satellite cells were treated with 10 ng/ml recombinant tissue inhibitor-1 of MMPs (TIMP-1) and subjected to treatments that induce activation in vitro, i.e., sodium nitroprusside (SNP) of an NO donor or mechanical cyclic stretch, the activation response was inhibited. In addition, conditioned medium generated by cultures treated with TIMP-1 plus SNP or mechanical stretch failed to activate cultured satellite cells and did not contain HGF. Moreover, NO(x) assay demonstrated that TIMP-1 does not impair NO synthase activity of stretched satellite cell cultures. Therefore, results from these experiments provide strong evidence that MMPs mediate HGF release from the matrix and that this step in the pathway is downstream from NO synthesis.
Yamada
Michiko
M
Department of Bioscience and Biotechnology, Kyushu University, Hakozaki, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan.
Tatsumi
Ryuichi
R
Kikuiri
Takashi
T
Okamoto
Shinpei
S
Nonoshita
Shinsuke
S
Mizunoya
Wataru
W
Ikeuchi
Yoshihide
Y
Shimokawa
Hiroaki
H
Sunagawa
Kenji
K
Allen
Ronald E
RE
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000201:enzymology*; D013314:Stress, Mechanical; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology
D020030:Nitric Oxide Donors; D019715:Tissue Inhibitor of Metalloproteinase-1; D009599:Nitroprusside; D009569:Nitric Oxide; D017228:Hepatocyte Growth Factor; D020782:Matrix Metalloproteinases