Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
Int J Mol Sci. 2021 Sep 19;22(18):10127. doi: 10.3390/ijms221810127.
Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and it is a known risk factor for hypertension. The upregulation of the renin-angiotensin system has been reported in IH, and the correlation between renin and CD38 has been noted. We exposed human HEK293 and mouse As4.1 renal cells to experimental IH or normoxia for 24 h and then measured the mRNA levels using a real-time reverse transcription polymerase chain reaction. The mRNA levels of () and were significantly increased by IH, indicating that they could be involved in the CD38-cyclic ADP-ribose signaling pathway. We next investigated the promotor activities of both genes, which were not increased by IH. Yet, a target mRNA search of the microRNA (miRNA) revealed both mRNAs to have a potential target sequence for miR-203. The miR-203 level of the IH-treated cells was significantly decreased when compared with the normoxia-treated cells. The IH-induced upregulation of the genes was abolished by the introduction of the miR-203 mimic, but not the miR-203 mimic NC negative control. These results indicate that IH stress downregulates the miR-203 in renin-producing cells, thereby resulting in increased mRNA levels of and , which leads to hypertension.
睡眠呼吸暂停综合征的特征是反复出现氧饱和度下降和再氧合（间歇性低氧[IH]），并且是高血压的已知危险因素。在 IH 中已经报道了肾素-血管紧张素系统的上调，并且已经注意到了肾素和 CD38 之间的相关性。我们将人 HEK293 和小鼠 As4.1 肾细胞暴露于实验性 IH 或常氧 24 小时，然后使用实时逆转录聚合酶链反应测量 mRNA 水平。IH 显著增加了 () 和 的 mRNA 水平，表明它们可能参与 CD38-环 ADP-核糖信号通路。我们接下来研究了这两个基因的启动子活性，IH 并未增加它们的活性。然而，对 microRNA (miRNA) 的靶 mRNA 搜索表明，这两个 mRNA 都有 miR-203 的潜在靶序列。与常氧处理的细胞相比，IH 处理的细胞中的 miR-203 水平显着降低。引入 miR-203 模拟物可消除 IH 诱导的基因上调，但 miR-203 模拟物 NC 阴性对照则不能。这些结果表明，IH 应激下调肾素产生细胞中的 miR-203，从而导致 mRNA 水平的 和 增加，从而导致高血压。
