15d-PGJ2 stimulates HO-1 expression through p38 MAP kinase and Nrf-2 pathway in rat vascular smooth muscle cells

15d-PGJ(2) a potent endogenous ligand for peroxisome proliferators activated receptor-gamma, is a cyclopentenone-type prostaglandin produced by many different types of cells. Pertinent to its effect on vascular smooth muscle cell (VSMC), antiproliferative effects have been most frequently reported. In the present study, we investigated the effect of 15d-PGJ(2) on HO-I expression that has been reported to inhibit VSMC proliferation. According to our data, 15d-PGJ2 significantly induced ROS/NO production and HO-1 expression in rVSMCs. We also observed 15d-PGJ(2)-,induced translocation of Nrf-2. In addition, ROS scavenger pretreatment suppressed 15 d-PGJ(2)-induced HO-1 expression while PPAR-gamma antagonist did not, suggesting nuclear translocation of Nrf-2 and subsequent HO-I expression was ROS dependent rather than PPAR gamma dependent. Furthermore, an inhibitor of p38 MAPK abolished 15d-PGJ(2)-induced HO-1 expression. These data suggest that 15d-PGJ(2)-induced up-regulation of HO-I is independent of PPAR-gamma but dependent of ROS and p38 MAPK pathway. The present study reports for the first time that 15d-PGJ2 induces HO-I expression possibly using Nrf-2 pathway as a response to ROS in VSMCs. (c) 2007 Elsevier Inc. All rights reserved.