OSTEOPONTIN EXPRESSION IN THE KIDNEY DURING UNILATERAL URETERAL OBSTRUCTION

Osteopontin is a bone protein also expressed in other tissues. Increas ed osteopontin is thought to be associated with tissue inflammation. W e used immunocytochemical analyses and polymerase chain reaction ampli fication of mRNA to examine osteopontin expression and regulation in u nilateral ureteral obstruction (UUO) in rats, a model of inflammatory kidney disease. In the obstructed kidney, osteopontin mRNA and protein were significantly increased. The increase reached 4-fold after 1 day of UUO and persisted at this level for the 5-day duration of UUO. Imm unocytochemical analyses showed increased osteopontin protein in tubul ar cells of the obstructed kidney cortex from days 1 through 5 of UUO. No such significant increase was apparent in the glomerulus or inters titium. Increased osteopontin mRNA and protein likewise occurred in th e tubular cells of the obstructed kidney of rats that had undergone wh ole-body irradiation to eliminate macrophage infiltration into the exp erimental kidney. Purified osteopontin was found to be a chemoattracta nt for macrophages isolated from the rat peritoneum. Enalapril treatme nt, which decreases macrophage infiltration of the obstructed kidney, had no effect on the increase in osteopontin mRNA but significantly at tenuated the increase in protein in tubular cells. Western blot analys is of whole cortical homogenates revealed that the osteopontin antibod y recognized one protein of 67 kD. The amount of this protein was subs tantially decreased in kidney homogenates obtained from enalapril-trea ted compared to untreated animals. Increased osteopontin synthesis may , therefore, contribute in part to the inflammatory response that char acterizes obstructive nephropathy.