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.
Lelongt
Brigitte
B
Unité INSERM 489 and Université Paris 6, Hôpital Tenon, Paris, France.
Ronco
Pierre
P
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000473:pathology / Q000503:physiopathology*; D005342:Fibrinolysis; D007107:Immune System / Q000503:physiopathology; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype
D007375:Interleukin-1; D016753:Interleukin-10; D020780:Matrix Metalloproteinase 9