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Upregulation of Reg IV and Hgf mRNAs by Intermittent Hypoxia via Downregulation of microRNA-499 in Cardiomyocytes.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 Oct 17; Vol. 23 (20). Date of Electronic Publication: 2022 Oct 17. - Publication Year :
- 2022
-
Abstract
- Sleep apnea syndrome (SAS) is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and is a risk factor for cardiovascular disease (CVD) and insulin resistance/Type 2 diabetes. However, the mechanisms linking IH stress and CVD remain elusive. We exposed rat H9c2 and mouse P19.CL6 cardiomyocytes to experimental IH or normoxia for 24 h to analyze the mRNA expression of several cardiomyokines. We found that the mRNA levels of regenerating gene IV ( Reg IV ) and hepatocyte growth factor ( Hgf ) in H9c2 and P19.CL6 cardiomyocytes were significantly increased by IH, whereas the promoter activities of the genes were not increased. A target mRNA search of microRNA (miR)s revealed that rat and mouse mRNAs have a potential target sequence for miR-499. The miR-499 level of IH-treated cells was significantly decreased compared to normoxia-treated cells. MiR-499 mimic and non-specific control RNA (miR-499 mimic NC) were introduced into P19.CL6 cells, and the IH-induced upregulation of the genes was abolished by introduction of the miR-499 mimic, but not by the miR-499 mimic NC. These results indicate that IH stress downregulates the miR-499 in cardiomyocytes, resulting in increased levels of Reg IV and Hgf mRNAs, leading to the protection of cardiomyocytes in SAS patients.
- Subjects :
- Rats
Mice
Animals
Myocytes, Cardiac metabolism
Up-Regulation
RNA, Messenger genetics
RNA, Messenger metabolism
Hepatocyte Growth Factor genetics
Hepatocyte Growth Factor metabolism
Down-Regulation genetics
Cell Hypoxia genetics
Hypoxia genetics
Hypoxia metabolism
Oxygen metabolism
Diabetes Mellitus, Type 2 metabolism
MicroRNAs genetics
MicroRNAs metabolism
Cardiovascular Diseases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 36293268
- Full Text :
- https://doi.org/10.3390/ijms232012414