Significance of increase in aquaporin 5 expression in respiratory system

O_2和CO_2气体通过质膜的输送对肺泡空间和血流之间维持正常呼吸至关重要。我们之前的研究表明，水通道蛋白（AQPs）促进了CO_2气体和水在质膜上的运动，并表明AQP表达的增加可能会促进肺泡内的气体交换。因此，在本研究中，我们首先研究了AQP5在肺泡上皮细胞中的表达机制。已经确定AQP5基因的启动子区域在没有AQP5的细胞类型中发生甲基化，而在肺泡I型细胞中发生去甲基化。AQP5 DNA的甲基化显著降低其转录活性和与Sp1转录因子的结合。我们还发现全反式维甲酸是一种新的AQP5诱导剂。维甲酸通过激活Sp1增加AQP5的转录。此外，我们还研究了一氧化氮（NO）对AQP5活性的影响，一氧化氮是一种重要的炎症介质。NO通过s -亚硝基化AQP5水孔中半胱氨酸残基降低AQP5活性。最终，我们制备了稳定表达AQP5的CHO细胞。未加AQP5的CHO细胞生长形态与对照组相同。但缺氧诱导的细胞凋亡明显少于对照组。有趣的是，葡萄糖剥夺在两种细胞中同样诱导凋亡，这表明AQP5增加气体代谢可能抑制缺氧诱导的AQP5表达细胞凋亡。这些发现有助于考虑在各种呼吸系统疾病中加强肺泡-血液屏障气体交换的新策略。

O_2 and CO_2 gas transport through plasma membrane is important to maintain normal respiration between alveolar space and blood flow. We have previously indicated that aquaporins (AQPs) enhances movement of CO_2 gas, as well as water, across plasma membrane, and suggested that the increase in AQP expression might enhance gas exchange at alveoli. In this study, therefore, we first examined the mechanism of AQP5 expression in alveolar epithelial cells. It has been defined that promoter region of AQP5 gene was methylated in the cell types without AQP5, whereas it was demethylated in alveolar type I cells. The methylation of AQP5 DNA significantly decreased its transcriptional activity and the binding to Sp1 transcription factor. We have also found all-trans retinoic acid as a new AQP5 inducer. Retinoic acid increased AQP5 transcription through the activation of Sp1. In addition, we examined the effect of nitric oxide (NO), which is an important inflammatory mediator, on AQP5 activity. NO decreased AQP5 activity by S-nitrosylation of cystein residue in the water pore of AQP5.We finally, prepared CHO cells which stably express AQP5. The growth and morphology were same with those of control CHO cells without AQP5. However, the apoptosis induced by hypoxia was significantly less than that in control cells. Interestingly, glucose deprivation induced apoptosis equally in both cells, suggesting increased gas metabolism by AQP5 might inhibit hypoxia-induced apoptosis in AQP5-expressing cells. These findings are useful to consider the new strategies to enhance gas exchange at alveolar-blood barrier in various respiratory diseases.