Upregulation of Osteopontin in Ischemia-Induced Renal Failure in Rats: A Role for ET-1?☆

Abstract In this study, the involvement of osteopontin in a rat model of ischemia-induced acute renal failure (ARF) was evaluated. In unilaterally nephrectomized Sprague Dawley rats where the left artery was occluded for 30 min., plasma creatinine levels increased significantly within two hours following reperfusion indicating the onset of renal failure. Northern analysis of kidney cortical RNA from these rats showed a time-dependent increase in osteopontin mRNA expression that was significantly higher than sham-operated rats. Since endothelin-1 (ET-1) is implicated as a mediator of acute renal failure, we evaluated its effects on osteopontin expression in a rat mesangial cell-line. Data from in vitro studies indicated that endothelin-1 (ET-1) caused a modest but reproducible increase in osteopontin mRNA in these cells. While the signal for osteopontin upregulation in the rat model is not known, ET-1, which is known to be increased during ischemia, may contribute at least in part to this process.