Matrix Metalloproteinase 9 Protects Mice from Anti–Glomerular Basement Membrane Nephritis through Its Fibrinolytic Activity

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 extent of crescents and fibrin deposits. Circulating or deposited immunoglobulin G, interleukin (IL)-1β, 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.

• Publication year

  2001

• Venue

  Journal of Experimental Medicine

• Publication date

  2001-04-02

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1084/JEM.193.7.793PMID 11283152PMCID 2193369
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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