期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms21030999
关键词
obstructive sleep apnea; miR-21-5p; miR-23a-3p; apoptosis; intermittent hypoxia with re-oxygenation
资金
- Ministry of Science and Technology, Taiwan [NMRPG8F6071-6073/105-2314-B-182A-092-MY3/108-2314-B-182A129-MY3]
- [CMRPG8C1183/CMRPG8G0281/CMRPG8G0282/CMRPG8J0581/CMRPG8J0231]
The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-alpha pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-alpha gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-alpha gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including TNF-alpha, ELF2, NFAT5, HIF-2 alpha, IL6, IL6R, EDNRB, and TLR4-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.
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