We identified a novel gene, termed megsin, predominantly expressed in mesangial cells utilizing a 3′-directed regional cDNA library from cultured human mesangial cells. Megsin is a novel serine protease inhibitor (serpin), and the level of megsin RNA/protein expression is up-regulated in patients with IgA nephropathy or diabetic nephropathy, suggesting a link between megsin expression and the pathogenesis of mesangial expansion and/or proliferation. To assess the pathophysiological significance of megsin, we produced human megsin transgenic mice. Genetic manipulation of megsin engenders two elementary mesangial lesions, mesangial expansion and an increase in the number of mesangial cells.
- Diabetic nephropathy
- IgA nephropathy
- Mesangial expansion
- Serine protease inhibitor (serpin)