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Identification of miRNAs induced by low-dose methylmercury exposure and their roles in inflammatory responses using
Rika Matsuyama1, Athira Nandakumar1, Munekazu Yamakuchi2
1Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences.
Background:
Exposure to methylmercury (MeHg) is predominantly attributed to consumption of marine products. However, the general population is exposed to low MeHg levels, which can induce chronic inflammation. Although some MeHg-related microRNAs (miRNAs) have been reported, their functions remain elusive. The objective of this study was to identify the miRNAs induced by low-level MeHg exposure in a human endothelial cell line (HAECs). This study aimed to determine the specific miRNAs induced by low-level MeHg exposure using a HAECs as a potential novel and sensitive biomarker. The roles of miRNAs in inflammatory processes have been examined.
Methods:
Using HAECs, a miRNA microarray assay was performed to identify miRNAs with altered expression upon exposure to a non-cytotoxic MeHg level (0.1 and 1.5 µM). The expression patterns of interleukin-6 and -8, cyclooxygenase 2 (COX-2), RelB, and prostaglandin E2 (PGE2) were examined after transfection of the identified miRNAs with mimics/inhibitors.
Results:
Although the microarray assay identified six MeHg-specific miRNAs, miR-3613-5p, upregulated by 0.1 and 1.5 µM MeHg exposures, demonstrated the best reproducibility in HAECs. Transfection with the miR-3613-5p mimic enhanced the MeHg-induced inflammatory responses, including PGE2 and COX-2 protein levels, whereas the miR-3613-5p inhibitor suppressed these inflammatory responses.
Conclusion:
This study observed that miR-3613-5p is induced by low-dose MeHg exposure, plays a crucial role in the inflammatory process, and could serve as a novel and sensitive biomarker for low-level MeHg exposure.
Insights
Low-level methylmercury (MeHg) exposure induces miR-3613-5p in human endothelial cells, promoting inflammation. This microRNA shows potential as a sensitive biomarker for chronic MeHg exposure.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Biomarker Discovery
Background:
- Methylmercury (MeHg) exposure, primarily from seafood, can cause chronic inflammation even at low levels.
- MicroRNAs (miRNAs) are implicated in inflammatory processes, but their specific roles in MeHg toxicity are not fully understood.
- Human umbilical vein endothelial cells (HUVECs) are a relevant model for studying low-dose MeHg effects.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) induced by low-level methylmercury (MeHg) exposure in human endothelial cells.
- To investigate the functional role of identified miRNAs in MeHg-induced inflammatory responses.
- To evaluate the potential of these miRNAs as sensitive biomarkers for low-dose MeHg exposure.
Main Methods:
- Human endothelial cells (HAECs) were exposed to non-cytotoxic levels of methylmercury (MeHg) (0.1 and 1.5 µM).
- MicroRNA microarray assays were performed to identify differentially expressed miRNAs.
- Expression of inflammatory markers (IL-6, IL-8, COX-2, PGE2) was analyzed following miRNA mimic or inhibitor transfections.
Main Results:
- Six MeHg-responsive miRNAs were identified, with miR-3613-5p showing consistent upregulation at both exposure levels.
- Overexpression of miR-3613-5p exacerbated MeHg-induced inflammatory responses, increasing PGE2 and COX-2 levels.
- Inhibition of miR-3613-5p suppressed these inflammatory markers, indicating its pro-inflammatory role.
Conclusions:
- miR-3613-5p is significantly induced by low-dose methylmercury (MeHg) exposure in human endothelial cells.
- This miRNA plays a critical role in mediating MeHg-induced inflammatory processes.
- miR-3613-5p represents a promising novel and sensitive biomarker for detecting low-level MeHg exposure.
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