Matrix metalloproteinase-2 expression and promoter/enhancer activity in skeletal muscle atrophy.
Matrix metalloproteinase-2 (MMP-2) appears to be the dominant MMP activated during skeletal muscle atrophy. However, little is known about cell-specific regulatory mechanisms of MMP-2 transcription in vivo. In this study, we used a mouse model of muscle atrophy induced by complete Achilles tendon transection. Time-dependent muscle weight loss, nuclei density reduction, and extracellular matrix degeneration were observed consistently after Achilles tendon transection. Increased MMP-2 expression was confirmed at the mRNA and protein level. Experiments using transgenic mice with a MMP-2 promoter/enhancer reporter construct demonstrated markedly increased MMP-2 promoter/enhancer activity in atrophic skeletal muscle. Tissue-specific upregulation of MMP-2 promoter activity was observed not only in myocytes, but also in blood vessels, nerve, and fascia. The transcription factors c-Jun and FosB were expressed at high levels in atrophic muscle, suggesting a role in MMP-2 upregulation. These findings show that increased MMP-2 activity in disused atrophic muscle and supporting tissues is regulated, at least in part, by increased MMP-2 promoter/enhancer activity.
Skittone
Laura K
LK
San Francisco Veterans Affairs Medical Center, 4150 Clement Street (112), San Francisco, California 94121, USA.
Liu
Xuhui
X
Tseng
Alice
A
Kim
Hubert T
HT
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D002467:Cell Nucleus / Q000648:ultrastructure; D004742:Enhancer Elements, Genetic; D005109:Extracellular Matrix / Q000378:metabolism; D005205:Fascia / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D032342:Muscle Cells / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000098:blood supply / Q000294:innervation / Q000378:metabolism; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009417:Nerve Tissue / Q000378:metabolism; D009929:Organ Size; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2