Oxygen-dependent regulation of aquaporin-3 expression.
Oxygen-dependent regulation of aquaporin-3 expression.
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DOI：
10.2147/hp.s97681
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Zieseniss A
中科院分区：
文献类型：
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作者：
Hoogewijs D;Vogler M;Zwenger E;Krull S;Zieseniss A
本研究的目的是探讨水通道蛋白3（AQP 3）的表达是否在缺氧改变，以及是否缺氧诱导转录因子（HIF）-1调节缺氧表达。研究了L929纤维肉瘤细胞和来自缺氧小鼠的几种组织中AQP 3 mRNA的表达。对AQP 3启动子的计算分析显示，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。低氧可导致L929纤维肉瘤细胞AQP 3 mRNA表达增加。因此，shRNA介导的HIF-1α的敲低大大降低了AQP 3的缺氧诱导。此外，对吸入性缺氧小鼠器官的mRNA分析表明，肾脏中AQP 3的表达明显受缺氧诱导。总之，我们的研究结果表明，AQP 3的表达可以在转录水平上进行调节，AQP 3代表了一种新的HIF-1靶基因。
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.