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 nephro pathies. To investigate its role, we used a genetic approach. Adult MMP9-de ficient (MMP9(-/-)) mice showed normal renal histology and function at 3 mo . We investigated the susceptibility of 3-mo-old mice to the accelerated mo del of anti-glomerular basement membrane nephritis, in which fibrin is an i mportant 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 an d 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 requ ired for a novel protective effect on the development of fibrin-induced glo merular lesions.