Abstract
Sleep apnea syndrome (SAS) is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]) and is a risk factor for hypertension. Among several mechanisms of hypertension in IH, up-regulation of renin (Ren)-angiotensin system has been reported. However, the detailed mechanism of how IH increases Ren remains elusive. We exposed human embryonic renal HEK293 and mouse juxtaglomerular As4.1 cells either to IH or normoxia for 24 hours and then measured mRNA and protein levels by real-time RT-PCR, ELISA and Western blot. We found that the mRNA and protein levels of Ren and Cd38 were significantly increased by IH. Introduction of small interfering RNA against Cd38 and addition of cell permeable cyclic ADP-ribose (cADPR) antagonist, 8-bromo-cADPR, attenuated the IH-induced increases of Ren expression, indicating an essential role of the CD38-cADPR signal in Ren expression in response to IH. Promotor activities of Ren and Cd38 were not increased by IH, suggesting the up-regulation is caused by post-transcriptional mechanism. We found that both mRNAs have a potential target sequence for miR-203. The miR-203 level of IH-treated cells was significantly decreased compared to normoxia-treated cells. Thus, we introduced miR-203 mimic and non-specific control RNA (miR-203 mimic NC) into As4.1 cells, exposed the cells to IH/normoxia. The IH-induced up-regulation of the mRNA levels of Ren and Cd38 was abolished by introduction of the miR-203 mimic but not by the miR-203 mimic NC. These results indicate that IH stress down-regulates the miR-203 in Ren-producing cells, resulting in increased levels of Ren and Cd38 mRNAs, leading SAS patients to hypertension.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2393.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021