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Intermittent Hypoxia Up-Regulates CCL2 , RETN, and TNFα mRNAs in Adipocytes via Down-regulation of miR-452.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Apr 22; Vol. 20 (8). Date of Electronic Publication: 2019 Apr 22. - Publication Year :
- 2019
-
Abstract
- Sleep apnea syndrome (SAS), characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), is a risk factor for insulin resistance. Recently, IH is considered to independently cause adipose tissue inflammation/dysfunction, leading to worsening insulin resistance; however, the detailed mechanism remains unknown. We exposed mouse 3T3-L1 and human SW872 adipocytes to experimental IH or normoxia for 24 h, and analyzed mRNA expression of several adipokines. We found that the mRNA levels of RETN , TNFα , and CCL2 in SW872 and 3T3-L1 adipocytes were significantly increased by IH, whereas the promoter activities of these genes were not increased. A target mRNA search of microRNA (miR)s revealed that all human mRNAs have a potential target sequence for miR-452. The miR-452 level of IH-treated cells was significantly decreased compared to normoxia-treated cells. MiR-452 mimic and non-specific control RNA (miR-452 mimic NC) were introduced into SW872 cells, and the IH-induced up-regulation of the genes was abolished by introduction of the miR-452 mimic but not by the miR-452 mimic NC. These results indicate that IH stress down-regulates the miR-452 in adipocytes, resulting in increased levels of RETN , TNFα , and CCL2 mRNAs, leading to insulin resistance in SAS patients.
- Subjects :
- Animals
Cell Hypoxia genetics
Cell Line, Tumor
Chemokine CCL2 metabolism
Humans
Mice
Promoter Regions, Genetic
Resistin metabolism
Sleep Apnea, Obstructive genetics
Sleep Apnea, Obstructive metabolism
Transcriptional Activation
Tumor Necrosis Factor-alpha metabolism
Adipocytes metabolism
Chemokine CCL2 genetics
Gene Expression Regulation
MicroRNAs genetics
RNA Interference
Resistin genetics
Tumor Necrosis Factor-alpha genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31013606
- Full Text :
- https://doi.org/10.3390/ijms20081960