Role of inter-α-inhibitor and its related proteins in experimentally induced calcium oxalate urolithiasis. Localization of proteins and expression of bikunin gene in the rat kidney

Our earlier studies indicated that members of the inter-α-inhibitor (IαI) family of glycoproteins may play an important role in urolithiasis. Indeed bikunin, the light chain of IαI is a potent inhibitor of calcium oxalate crystallization. In order to understand this role, the distribution of IαI and its related proteins, as well as the expression of bikunin, were studied in normal and nephrolithic rats. In normal rats, IαI immunoreactivity was located mainly in proximal tubules. However, in nephrolithic rats, in addition to proximal tubules, the staining was intensively extended to tubules in the corricomedullary junction. Furthermore, by using polymerase chain reaction technique, we demonstrated that gene encoding for bikunin was activated in kidneys of nephrolithic rats. We have previously demonstrated increased staining for osteopontin in association with calcium oxalate crystal deposition in rat kidneys. Others have shown an increase in osteopontin production by renal epithelial cells on exposure to calcium oxalate crystals. Based on these observations we conclude that kidney cells possess an auto-defense system against calcium oxalate crystallization and stone formation in which members of the IαI family may be closely involved.