Kaneko Kentaro, Yagui Kazuo, Tanaka Asami, Yoshihara Kei, Ishikawa Kou, Takahashi Kazuo, Bujo Hideaki, Sakurai Kenichi, Saito Yasushi
Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Microvasc Res. 2008 Apr;75(3):297-301. doi: 10.1016/j.mvr.2007.12.003. Epub 2008 Jan 3.
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.
水通道蛋白1（AQP1）最初是从红细胞膜中纯化出来的，现在已知它是一种由渗透压驱动的水转运蛋白，在脑外的许多上皮细胞和内皮细胞中广泛表达。最近的几项研究表明，AQP1在增殖的肿瘤微血管中表达强烈，这表明AQP1可能在肿瘤血管生成中起重要作用。缺氧被认为是许多视网膜疾病（包括糖尿病性视网膜病变）新生血管形成的常见先兆，因此我们分析了在缺氧条件下培养的人视网膜血管内皮细胞中AQP1的表达模式和功能。在缺氧条件下，AQP1 mRNA和蛋白表达水平显著增加，而抑制VEGF信号传导并不影响AQP1的表达。为了研究AQP1对缺氧诱导的血管生成的影响，进行了管腔形成试验。使用小干扰RNA降低AQP1表达和抑制VEGF信号传导均显著抑制管腔形成，且这些作用具有相加性。因此，我们的数据表明，AQP1通过一种独立于VEGF信号通路的机制参与视网膜血管内皮细胞中缺氧诱导的血管生成。
