Hoogewijs David, Vogler Melanie, Zwenger Eveline, Krull Sabine, Zieseniss Anke
Institute of Physiology, University of Duisburg-Essen, Essen, Germany; Institute of Physiology, University of Zürich, Zürich, Switzerland.
Institute of Cardiovascular Physiology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.
Hypoxia (Auckl). 2016 Apr 21;4:91-97. doi: 10.2147/HP.S97681. eCollection 2016.
The purpose of this study was to investigate whether aquaporin-3 (AQP3) expression is altered in hypoxia and whether hypoxia-inducible transcription factor (HIF)-1 regulates the hypoxic expression. AQP3 mRNA expression was studied in L929 fibrosarcoma cells and in several tissues derived from mice that were subjected to hypoxia. Computational analysis of the AQP3 promoter revealed conserved HIF binding sites within close proximity to the translational start site, and chromatin immunoprecipitation assays confirmed binding of HIF-1α to the endogenous hypoxia response elements. Furthermore, hypoxia resulted in increased expression of AQP3 mRNA in L929 fibrosarcoma cells. Consistently, shRNA-mediated knockdown of HIF-1α greatly reduced the hypoxic induction of AQP3. In addition, mRNA analysis of organs from mice exposed to inspiratory hypoxia demonstrated pronounced hypoxia-inducible expression of AQP3 in the kidney. Overall, our findings suggest that AQP3 expression can be regulated at the transcriptional level and that AQP3 represents a novel HIF-1 target gene.
本研究的目的是调查水通道蛋白3（AQP3）在缺氧状态下的表达是否发生改变，以及缺氧诱导转录因子（HIF）-1是否调节缺氧状态下的表达。在L929纤维肉瘤细胞以及来自经历缺氧的小鼠的多种组织中研究了AQP3 mRNA的表达。对AQP3启动子的计算分析揭示了在翻译起始位点附近存在保守的HIF结合位点，染色质免疫沉淀试验证实HIF-1α与内源性缺氧反应元件结合。此外，缺氧导致L929纤维肉瘤细胞中AQP3 mRNA表达增加。同样，shRNA介导的HIF-1α敲低极大地降低了AQP3的缺氧诱导。此外，对暴露于吸气性缺氧的小鼠器官的mRNA分析表明，肾脏中AQP3有明显的缺氧诱导表达。总体而言，我们的研究结果表明，AQP3的表达可在转录水平上受到调节，并且AQP3代表一种新的HIF-1靶基因。
