Nomura Johji, Horie Ichiro, Seto Mayumi, Nagai Kazufumi, Hisatsune Akinori, Miyata Takeshi, Isohama Yoichiro
Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):1048-53. doi: 10.1016/j.bbrc.2006.10.159. Epub 2006 Nov 7.
Aquaporin-5 (AQP5) is a water-selective channel protein that is expressed in lacrimal glands, salivary glands, and distal lung. Several studies using AQP5 knockout mice have revealed that AQP5 plays an important role in maintaining water homeostasis in the lung. We report here that all-trans retinoic acid (atRA) increases plasma membrane water permeability, AQP5 mRNA and protein expression, and AQP5 promoter activity in MLE-12 cells. The promoter activation induced by atRA was diminished by mutation at the Sp1/Sp3 binding element (SBE), suggesting that the SBE mediates the effects of atRA. In addition, atRA increased the binding of Sp1 to the SBE without changing the levels of Sp1 in the nucleus. Taken together, our data indicate that atRA increases AQP5 expression through transactivation of Sp1, leading to an increase in plasma membrane water permeability.
水通道蛋白5（AQP5）是一种水选择性通道蛋白，在泪腺、唾液腺和肺远端表达。多项使用AQP5基因敲除小鼠的研究表明，AQP5在维持肺内水平衡方面发挥着重要作用。我们在此报告，全反式维甲酸（atRA）可增加MLE-12细胞的质膜水通透性、AQP5 mRNA和蛋白表达以及AQP5启动子活性。atRA诱导的启动子激活在Sp1/Sp3结合元件（SBE）处发生突变时减弱，这表明SBE介导了atRA的作用。此外，atRA增加了Sp1与SBE的结合，而不改变细胞核中Sp1的水平。综上所述，我们的数据表明，atRA通过Sp1的反式激活增加AQP5表达，从而导致质膜水通透性增加。
