Possible role of Ets-1 and MMP-1 in matrix remodeling in experimental cisplatin nephropathy.

Cisplatin is an effective antitumor drug, but nephrotoxicity has restricted its clinical use. Renal interstitial fibrosis is a major complication of cisplatin treatment, due to the increased accumulation of extracellular matrix (ECM) proteins. Ets-1 protein plays a role in matrix remodeling by regulating matrix-degrading enzymes. We studied the role of Ets-1, matrix metalloproteinase-1 (MMP-1), and interstitial collagen (type III) in experimental cisplatin nephropathy. Wistar rats ( n = 24) were treated with cisplatin (6 mg/kg), and killed on days 3, 7, and 14, along with control rats. By immunohistochemistry, a significant increase ( P < 0.02) in the number of Ets-1-positive cells (40.09 +/- 1.52) was detected in kidneys of cisplatin-treated rats on day 3, compared with the number in control rat kidneys (29.80 +/- 0.13). The number of Ets-1-positive cells decreased in kidneys from cisplatin-treated rats on days 7 (10.93 +/- 1.20) and 14 (12.16 +/- 0.60). The expression of MMP-1 showed a similar pattern, increasing on day 3, but decreasing on days 7 and 14. The decreased levels of Ets-1 and MMP-1 were associated with increased interstitial accumulation of collagen in kidneys of cisplatin-treated rats on day 14. Molecular interactions among Ets-1, MMP-1, and type III collagens might play a role in matrix remodeling in cisplatin nephropathy.