Moghadasi, Mona and Taherimoghaddam, Mozhgan and Babaeenezhad, Esmaeel and Birjandi, Mehdi and Kaviani, Mozhgan and Moradi Sarabi, Mostafa (2024) MicroRNA-34a and promoter methylation contribute to peroxisome proliferator-activated receptor gamma gene expression in patients with type 2 diabetes. Diabetes & metabolic syndrome.
Full text not available from this repository.Abstract
Aims: This study aimed to investigate the roles of DNA methylation and miR-34a in the regulation of peroxisome proliferator-activated receptor gamma (PPARγ) in patients with type 2 diabetes (T2D). Methods: We investigated the methylation status of four regions of the PPARγ promoter and PPARγ expression in a panel of 84 T2D patients using methylation-specific PCR (MSP) and RT-qPCR, respectively. Moreover, we quantified DNA methyltransferases (DNMTs) expression and global DNA methylation levels by RT-qPCR and ELISA, respectively. We measured the expression levels of miR-34a and protein expression of PPARγ by stem-loop RT-qPCR and ELISA, respectively. Results: We found significant DNA hypermethylation in the R2 and R3 regions of the PPARγ promoter in people with diabetes. Functionally, this was associated with a significant reduction in PPARγ expression. In addition, we observed a significant increase in 5-methylcytosine levels in people with diabetes. A marked increase in circulating miR-34a in the early stages of T2D (up to 10 years) and a significant decrease in circulating miR-34a with increasing diabetes duration from 10 years after the onset of diabetes. Interestingly, upregulation of DNA methyltransferases 1 (DNMT1), DNMT3A, and DNMT3B was observed in people with diabetes, and the average expression of DNMTs was negatively correlated with circulating miR-34a levels. In contrast, the serum protein level of PPARγ, a direct target of miR-34a, increased considerably with diabetes duration and showed a negative correlation with circulating miR-34a, cholesterol, triglyceride, and low-density lipoprotein. Conclusion: PPARγ promoter hypermethylation and miR-34a upregulation are associated with T2D pathogenesis through PPARγ dysregulation. Keywords: DNA methylation; Gene expression; PPARγ; Type 2 diabetes; miR-34a.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) R Medicine > RC Internal medicine R Medicine > RZ Other systems of medicine |
| Divisions: | Faculty of Medicine, Health and Life Sciences > School of Medicine |
| Depositing User: | lorestan university |
| Date Deposited: | 14 Dec 2024 11:37 |
| Last Modified: | 14 Dec 2024 11:37 |
| URI: | http://eprints.lums.ac.ir/id/eprint/4959 |
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