Abstract
The present study aimed to explore the role of kelch-like ECH-associated protein-1 (Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway in regulating heme oxygenase-1 (HO-1) expression in adverse outcomes of preeclampsia (PE). Adult Wistar rats, HTR-8/SVneo and hESC cells were used for models in vitro and in vivo, respectively. Inhibition of Nrf-2 could slightly reduce the elevation of systolic blood pressure (SBP) and urinary protein in PE rats. The percentages of dead fetuses during pregnancy and within seven days of birth were decreased by Nrf-2 inhibitor. There was no significant effect on the pathology and HO-1 expression of Nrf-2 in placental tissue. Deficiency of Nrf-2 increased significantly the levels of chemokine 2 (CCL2), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), angiotensin II receptor type 1 (AT1R) and reactive oxygen species (ROS) in the embryonic tissues. Knockdown of Nrf-2 suppressed cell proliferation, improved cell apoptosis and invasion with an increase of ROS and HO-1, but the effect on cells apoptosis was greater. Activation of Nrf-2 pathway could reduce oxidative stress in PE rats and trophoblast cells induced by Ang II, and enhance the adverse outcome of PE via increasing HO-1. Nrf-2 silence reshaped blood vessels and achieved the effect of treating PE. Our results might provide theoretical guidance for the application of Nrf-2 in the treatment of PE.