Strong association between fibronectin accumulation and lowered cathepsin B activity in glomeruli of diabetic rats

In diabetic nephropathy the progressive accumulation of extracellular matrix (ECM) proteins results from an imbalance between synthetic and degradative pathways. While the role of the different matrix metalloproteinases in the impaired ECM degradation has been studied in detail, the function of lysosomal cysteine proteinases has not received adequate attention. The aim was to investigate a potential relationship between the accumulated ECM protein fibronectin (FN), and cathepsin B activity in isolated glomeruli of diabetic and healthy rats. Twenty male Wistar rats were included: 10 healthy and 10 with streptozotocin-induced diabetes. After 6 weeks, the experiments were terminated. In the homogenates of isolated glomeruli, FN content and cathepsin B activity were measured by ELISA or spectrofluorometry. FN was also analyzed by immunohistochemistry. Diabetic rats showed a significant rise of systolic blood pressure, impaired renal function and an enhanced urinary excretion of albumin, FN and cathepsin B. In the homogenates of the isolated glomeruli the ratios of FN/protein and FN/DNA showed a trend to higher values, while the ratios of cathepsin B/protein and cathepin B/DNA were reduced. The strong positive association between intraglomerular FN content and cathepsin B activity of in both groups suggests that this cysteine proteinase contributes to the degradation of the ECM protein FN. The much higher FN content in DN rats associated with an inadequate cathepsin B activity implies the role of an insufficient FN degradation by cathepsin B and other proteinases.