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Nephrol Dial Transplant (2002) 17: 28-31
© 2002 European Renal Association-European Dialysis and Transplant Association

Glomerular Development and Pathology

Role of matrix metalloproteinases in kidney development and glomerulopathy: lessons from transgenic mice

Brigitte Lelongt and Pierre Ronco

Unité INSERM 489 and Université Paris 6, Hôpital Tenon, Paris, France

Abstract

Matrix metalloproteinase-9 (MMP9) is required for renal organogenesis in vitro and is increased in various nephropathies. We analysed the renal phenotype of MMP9-deficient mice and their susceptibility to a murine model of proliferative glomerulonephritis. MMP9 deficiency resulted in adult mice in a 12% nephronic reduction. Histological appearance and renal function of these mice was normal up to 12 months, at which time histological lesions appeared. In addition, glomerulonephritis was more severe in MMP9-deficient mice than in their control 3-month-old mates. In particular, the extent of crescent formation and fibrin deposition was greater, which led us to show that fibrin is a critical substrate for MMP9. These data provide the first demonstration in vivo that MMP9 is required for nephron mass formation and renal function in elderly mice, and further evidence of a novel protective effect of MMP9 on the development of fibrin-induced glomerular lesions.

Keywords: fibrinogen; glomerulonephritis; kidney development; matrix metalloproteinase

Notes

Correspondence and offprint requests to: B. Lelongt, Unité INSERM 489 and Université Paris 6, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France.


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