Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 193, Issue 7, Pages 793-802Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.193.7.793
Keywords
matrix metalloproteinase; kidney; fibrin; crescent; proteinuria
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Funding
- NCI NIH HHS [CA72006, P01 CA072006] Funding Source: Medline
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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.
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