Aquaporin 1 is required for hypoxia-inducible angiogenesis in human retinal vascular endothelial cells

Aquaporin 1 (AQP1) was first purified from red blood cell membranes and is now known to be an osmolarity-driven water transporter that is widely expressed in many epithelial and endothelial cells outside the brain. Several recent studies have shown strong expression of AQP1 in proliferating tumor microvessels, suggesting that AQP1 may have an important role in tumor angiogenesis. Hypoxia is thought to be a common precursor to neovascularization in many retinal diseases, including diabetic retinopathy, and therefore we analyzed the expression pattern and function of AQP1 in human retinal vascular endothelial cells cultured under hypoxic conditions. The levels of AQP1 mRNA and protein expression significantly increased under hypoxia, and inhibition of VEGF signaling did not affect AQP1 expression. To examine the effect of AQP1 on hypoxia-inducible angiogenesis, a tube formation assay was performed. Reduction of AQP1 expression using siRNA and inhibition of VEGF signaling both significantly inhibited tube formation, and these effects were additive. Therefore, our data suggest that AQP1 is involved in hypoxia-inducible angiogenesis in retinal vascular endothelial cells through a mechanism that is independent of the VEGF signaling pathway. (c) 2008 Elsevier Inc. All rights reserved.