Matrix metalloproteinase 9 protects mice from anti-glomerular basement membrane nephritis through its fibrinolytic activity

被引:114
作者
Lelongt, B
Bengatta, S
Delauche, M
Lund, LR
Werb, Z
Ronco, PM
机构
[1] Hop Tenon, INSERM, U489, F-75020 Paris, France
[2] Univ Paris 06, F-75020 Paris, France
[3] Finsen Lab, DK-2100 Copenhagen, Denmark
[4] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
关键词
matrix metalloproteinase; kidney; fibrin; crescent; proteinuria;
D O I
10.1084/jem.193.7.793
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Matrix metalloproteinase (MMP)9/gelatinase B is increased in various nephropathies. To investigate its role, we used a genetic approach. Adult MMP9-deficient (MMP9(-/-)) mice showed normal renal histology and function at 3 mo. We investigated the susceptibility of 3-mo-old mice to the accelerated model of anti-glomerular basement membrane nephritis, in which fibrin is an important mediator of glomerular injury and renal impairment. Unexpectedly, nephritis was more severe in MMP9(-/-) than in control mice, as attested by levels of serum creatinine and albuminuria, and the er;tmt of crescents and fibrin deposits. Circulating or deposited immunoglobulin G, interleukin (IL)-1 beta, or IL-10 were the same in MMP9(-/-) and MMP9(+/+) mice. However, we found that fibrin is a critical substrate for MMP9, and in its absence fibrin accumulated in the glomeruli. These data indicate that MMP9 is required for a novel protective effect on the development of fibrin-induced glomerular lesions.
引用
收藏
页码:793 / 802
页数:10
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