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