OSTEOPONTIN EXPRESSION IN ANGIOTENSIN-II-INDUCED TUBULOINTERSTITIAL NEPHRITIS

Osteopontin is an arginine-glycine-aspartate (RGD) containing secreted phosphoprotein recently shown to stimulate a local macrophage influx when injected subcutaneously in mice. We examined the effect of angiot ensin II infusion on renal injury and osteopontin expression in the ra t kidney by in situ hybridization and immunohistochemistry. Preceding pathologic changes in tubular and interstitial cells, a dramatic incre ase in renal osteopontin protein and mRNA levels was observed primaril y in epithelial cells of the distal tubules, collecting ducts and Bowm an's capsule. Although both cortex and medulla showed increased osteop ontin levels, the effect was most pronounced in the renal cortex which normally showed very little constitutive osteopontin expression. Inte restingly, regions of the kidney expressing high osteopontin levels co rrelated with sites of monocyte/macrophage accumulation. These observa tions, coupled with recent findings that osteopontin may be a pro-infl ammatory protein, suggests that osteopontin over-expression may facili tate monocyte/macrophage accumulation at the sites of renal tubulointe rstitial injury.