Glomerular metalloprotease activity modulates the development of focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a common outcome of a variety of renal diseases. Among laboratory animals both puromycin aminonucleoside (PAN) and hypertension produce a similar histological pattern. Since mesangial expansion is a precursor of FGS and decreased degradation of matrix can cause expansion of mesangium we studied the glomerular matrix metalloprotease activities in the development of FSGS. Dahl salt sensitive (SS) and salt resistant (SR) rats were fed 8% salt diet for six weeks. Kidney biopsy showed features of FSGS in SS rats. Glomeruli were isolated and metalloprotease activity was measured. Sprague-Dawley rats were administered subcutaneously either saline (S) or saline containing PAN (1.67 mg/100 g B. W.) daily for 7 days. Kidney biopsy was done at day 7 and the isolation of glomeruli was performed at day 10 and at 6 weeks. Renal histology showed features of FSGS in PAN rats at 6 weeks. Glomerular metalloprotease activity was decreased in SS (SR, 148 +/- 12 vs. SS, 73 +/- 9 cpm/microgram protein, p < 0.01) as well as in PAN rats (S, 31 +/- 5 vs. PAN, 12 +/- 1 cpm/microgram protein, p < 0.01). These results suggest that decreased glomerular metalloprotease activity may play a role in the development of FSGS in SS and PAN rats.