RGD Reference Report - 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury. - Rat Genome Database

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

Authors: Wang, YF  Fan, ZK  Cao, Y  Yu, DS  Zhang, YQ  Wang, YS 
Citation: Wang YF, etal., Brain Res. 2011 Jan 25;1370:220-6. Epub 2010 Nov 16.
RGD ID: 5148013
Pubmed: PMID:21092735   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2010.11.016   (Journal Full-text)

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-1alpha (HIF-1alpha), 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-1alpha. 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-1alpha after SCI through the mechanisms that were dependent and independent of the VEGF signaling pathway, respectively. And the inhibitor of HIF-1alpha is a novel promising therapeutic agent for human SCI-induced edema in the future.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Spinal Cord Injuries  ISOAqp1 (Rattus norvegicus)5148013; 5148013 RGD 
Spinal Cord Injuries  ISOAqp4 (Rattus norvegicus)5148013; 5148013 RGD 
Spinal Cord Injuries  IEP 5148013; 5148013 RGD 
Spinal Cord Injuries  ISOHif1a (Rattus norvegicus)5148013; 5148013protein:increased expression:spinal cordRGD 
Spinal Cord Injuries  IEP 5148013; 5148013protein:increased expression:spinal cordRGD 
Spinal Cord Injuries  ISOVegfa (Rattus norvegicus)5148013; 5148013protein:increased expression:spinal cordRGD 

Objects Annotated

Genes (Rattus norvegicus)
Aqp1  (aquaporin 1)
Aqp4  (aquaporin 4)
Hif1a  (hypoxia inducible factor 1 subunit alpha)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Aqp1  (aquaporin 1)
Aqp4  (aquaporin 4)
Hif1a  (hypoxia inducible factor 1, alpha subunit)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
AQP1  (aquaporin 1 (Colton blood group))
AQP4  (aquaporin 4)
HIF1A  (hypoxia inducible factor 1 subunit alpha)
VEGFA  (vascular endothelial growth factor A)


Additional Information