Glomerular scarring (glomerulosclerosis), a slowly progressive disease, is the most common cause of kidney failure. Current models of glomerulosclerosis (GS) have yielded little information about the cellular and molecular abnormalities that are critical in the initiation and progression of this disease since they most often are models of acute inflammation. For this reason we constructed models of slowly progressive disease of a non-inflammatory type. The complexity of the kidney and glomerulus makes isolation and examination of pure cultured populations of glomerular cells an attractive method for beginning to address the pathogenesis of GS. Mice transgenic for the early region of simian virus 40 (SV40) and for growth hormone develop slowly progressive GS. As there are no evident extrarenal sources of injury, and since expression of the foreign DNA has been documented to occur in whole kidney, we postulated that the glomerular disease may be secondary to expression of the foreign DNA by glomerular cells in vivo. We have isolated lines of glomerular endothelial, mesangial, and epithelial cells from transgenic mice and have isolated pure cultures of mesangial, endothelial cells and epithelial cells from their normal litter-mates. Our data from this in vivo model indicates that proliferation of glomerular cells is an early event in the development of GS in transgenic mice.
