[Studies on initiation and progression of focal glomerular sclerosis in rats]

In order to clarify the mechanisms of the initiation and progression of focal glomerular sclerosis (FGS), we investigated changes in the mesangial function or qualitative changes in the extracellular matrix of mesangium in puromycin aminonucleoside (PAN)-induced FGS in rats. At first, we investigated that the relationship between the progression of FGS and mesangial function. In order to evaluate the mesangial function, rats received the i.v. injection of colloidal carbon (C. C.) (20 or 30 mg/100 g). Results obtained from this experiment suggest that the progression of glomerular sclerosis may be related to changes in mesangial function. Furthermore, results suggest that the abnormality of the extracellular matrix may lead to changes in mesangial function and the progression of glomerular sclerosis. Therefore, in the next experiment, the proteoglycans (PGs), one of the components of extracellular matrix, were analyzed by the column chromatography to clarify qualitative changes in the PGs such as the molecular size and charge density. Results obtained from this experiment indicate that the sclerotic glomeruli synthesize the PGs with different molecular size and charge density from normal glomeruli. It is concluded from these experiments that the abnormality of the mesangial function and the synthesis of PGs, the components of the extracellular matrix, may lead to the progression of FGS. Namely, the qualitatively altered PGs may cause abnormal interactions with other components of matrix, which lead to changes in mesangial function, death of mesangial cell and the progression of FGS.