Role of gelatinases in disuse-induced skeletal muscle atrophy.
Gelatinases are a subgroup of the family of matrix metalloproteinases, which contains two members-gelatinase A and B. These enzymes play an important role in basement membrane homeostasis. Previous studies have associated basement membrane degradation with skeletal muscle atrophy. However, the specific contribution of gelatinases to the pathobiology of muscle atrophy remains unknown. In this study we examined the specific roles of gelatinase A and B in disuse-induced skeletal muscle atrophy using knockout mice. Although both gelatinase A and B are highly upregulated in disused muscle, only gelatinase A null mice had significantly reduced muscle atrophy as compared to wildtype littermates. Type IV collagen and laminin, two major components of basement membrane, were relatively well-preserved in disused muscle in gelatinase A null mice, but not in gelatinase B null mice. These findings suggest that gelatinase A, and not gelatinase B, plays a critical role in disuse-induced skeletal muscle atrophy.
San Francisco Veterans Affairs Medical Center, Department of Veterans Affairs, 4150 Clement Street (112), San Francisco, California 94121, USA.
Xuhui
X
Liu
David J
DJ
Lee
Laura K
LK
Skittone
Kyle
K
Natsuhara
Hubert T
HT
Kim
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D024141:Collagen Type IV / Q000378:metabolism; D004195:Disease Models, Animal; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D013710:Tendons / Q000601:surgery
D024141:Collagen Type IV; D007797:Laminin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9