Involvement of androgen receptor (AR)/microRNA-21 axis in hypoxia/reoxygenation-induced apoptosis of mouse renal tubular epithelial cells.

The function of androgen receptor (AR)/microRNA-21 (miR-21) axis in tumor development was well investigated. However, the roles of the axis performed in hypoxia/reoxygenation (H/R)-induced apoptosis of mouse renal tubular epithelial cells (RTECs) is not known. In this study, H/R-induced apoptosis of RTECs was established to evaluate the role of miR-21-AR axis. The protocol of 8-h hypoxia and 24-h reoxygenation were selected to produce H/R injury. Our data showed that H/R increased miR-21 and caspase-3 expression, reduced the expression AR and programmed cell death protein 4 (PDCD4). By contrast, AR-siRNA increased H/R-induced apoptosis, and promoted caspase-3 expression, but reduced PDCD4 expression (vs. H/R group). pre-miR-21 reduced, while antagomiR-21 promoted apoptosis and PDCD4 expression in H/R-induced RTECs. Moreover, pre-miR-21 promoted, while antagomiR-21 reduced caspase-3 expression in H/R-induced RTECs. Together, H/R increased miRNA-21 and reduced AR expression, then regulating PDCD4- and caspase-3-dependent apoptosis. AR/miR-21 axis could be a potential therapeutic target for the kidney ischemia injury. AJTR