Intraglomerular fibronectin accumulation and degradation in obese Zucker rats

The obese Zucker rat is a classic model of non-immune mediated spontaneous focal glomerulosclerosis. An important initiating hallmark of glomerulosclerosis in this model is mesangial matrix expansion. Fibronectin, a highly biologically active glycoprotein, is a normal constituent of mesangial extracellular matrix. Using a quantitative method based on enzyme immunoassay we assessed the intraglomerular fibronectin content and its degradation in obese Zucker rats and their lean littermates. In the obese Zucker rats the glomerular fibronectin content was significantly higher in comparison to the controls (88 +/- 6 vs 48 +/- 4 ng/10(3) glomeruli). Furthermore, proteinase activity against fibronectin was significantly reduced in the glomeruli of obese Zucker rats when compared to control animals (at pH 5.4: 186 +/- 6 U/mg protein vs 286 +/- 14 U/mg protein, at pH 7.4: 152 +/- 12 U/mg protein vs 193 +/- 12 U/mg protein). These data demonstrate that in obese Zucker rats there is a glomerular accumulation of fibronectin which we propose is at least partly due to diminished proteolytic digestion. Whether accumulation of intraglomerular fibronectin contributes to progressive glomerulosclerosis remains a matter of debate.