2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury

The study investigated the mechanism of the up-regulation of aquaporin-4 (AQP4) and aquaporin-1 (AQP1) expression induced by spinal cord injury (SCI). Using adult rat spinal cord injury model, it was found that up-regulation of hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), AQP4, and AQP1 in response to spinal cord injury was greatly antagonized by 2-methoxyestradiol (2ME2), which can post-transcriptionally inhibit the expression of HIF-1 alpha. VEGF alone significantly increased the extravasation of Evans blue and up-regulated the levels of AQP4 protein expression in the injured spinal cord issue, but the levels of AQP1 expression were not significantly changed. Taken together, our results suggest that expression of AQP4 and AQP1 is correlated with up-regulation of HIF-1 alpha after SCI through the mechanisms that were dependent and independent of the VEGF signaling pathway, respectively. And the inhibitor of HIF-1 alpha is a novel promising therapeutic agent for human SCI-induced edema in the future. (C) 2010 Published by Elsevier B.V.