title: 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury.
abstract: 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-1α (HIF-1α), 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-1α. 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-1α after SCI through the mechanisms that were dependent and independent of the VEGF signaling pathway, respectively. And the inhibitor of HIF-1α is a novel promising therapeutic agent for human SCI-induced edema in the future.
authors.affiliation: The First Affiliated Hospital, China Medical University, Department of Orthopaedics, the Nanjing Bei Street No 155, Heping District, Shen yang, Liaoning Province 110001, PR China. wyf_doctor@163.com
authors.forename: Yan-feng
authors.initials: YF
authors.lastname: Wang
authors.forename: Zhong-kai
authors.initials: ZK
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: De-shui
authors.initials: DS
authors.lastname: Yu
authors.forename: Yu-qiang
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Yan-song
authors.initials: YS
authors.lastname: Wang
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D051398:Aquaporin 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051401:Aquaporin 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C496022:Aqp1 protein, rat; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D018696:Neuroprotective Agents; D050257:Tubulin Modulators; D051398:Aquaporin 1; D004958:Estradiol; D000077584:2-Methoxyestradiol