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MiR-146a Is Mutually Regulated by High Glucose-Induced Oxidative Stress in Human Periodontal Ligament Cells
Chihiro Fumimoto1, Nobuhiro Yamauchi1, Emika Minagawa1
1Department of Periodontology, Osaka Dental University, 8-1, Kuzuhahanazono-cho, Hirakata 573-1121, Osaka, Japan.
Abstract:
The high-glucose conditions caused by diabetes mellitus (DM) exert several effects on cells, including inflammation. miR-146a, a kind of miRNA, is involved in inflammation and may be regulated mutually with reactive oxygen species (ROS), which are produced under high-glucose conditions. In the present study, we used human periodontal ligament cells (hPDLCs) to determine the effects of the high-glucose conditions of miR-146a and their involvement in the regulation of oxidative stress and inflammatory cytokines using Western blotting, PCR, ELISA and other methods. When hPDLCs were subjected to high glucose (24 mM), cell proliferation was not affected; inflammatory cytokine expression, ROS induction, interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) expression increased, but miR-146a expression decreased. Inhibition of ROS induction with the antioxidant N-acetyl-L-cysteine restored miR-146a expression and decreased inflammatory cytokine expression compared to those under high-glucose conditions. In addition, overexpression of miR-146a significantly suppressed the expression of the inflammatory cytokines IRAK1 and TRAF6, regardless of the glucose condition. Our findings suggest that oxidative stress and miR-146a expression are mutually regulated in hPDLCs under high-glucose conditions.
Insights
High glucose in diabetes mellitus increases oxidative stress and inflammation in human periodontal ligament cells. This study reveals that miR-146a counteracts these effects, suggesting a mutual regulation between oxidative stress and miR-146a.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Diabetes mellitus (DM) induces high-glucose conditions, promoting cellular inflammation.
- MicroRNA-146a (miR-146a) plays a role in inflammation and may interact with reactive oxygen species (ROS).
- ROS are elevated under high-glucose conditions, contributing to cellular damage.
Purpose of the Study:
- To investigate the impact of high glucose on miR-146a expression in human periodontal ligament cells (hPDLCs).
- To explore the role of miR-146a in regulating oxidative stress and inflammatory cytokines under high-glucose conditions.
- To determine the relationship between miR-146a and ROS in hPDLCs.
Main Methods:
- Human periodontal ligament cells (hPDLCs) were exposed to high-glucose conditions (24 mM).
- Expression levels of miR-146a, ROS, and inflammatory cytokines (IRAK1, TRAF6) were measured using Western blotting, PCR, and ELISA.
- The effects of the antioxidant N-acetyl-L-cysteine and miR-146a overexpression were assessed.
Main Results:
- High glucose did not affect hPDLC proliferation but increased inflammatory cytokine expression, ROS induction, IRAK1, and TRAF6.
- miR-146a expression decreased under high-glucose conditions.
- Antioxidant treatment restored miR-146a levels and reduced inflammation.
- Overexpression of miR-146a suppressed IRAK1 and TRAF6 expression.
Conclusions:
- Oxidative stress and miR-146a expression are mutually regulated in hPDLCs under high-glucose conditions.
- miR-146a acts as a protective factor against high-glucose-induced oxidative stress and inflammation.
- Targeting the miR-146a pathway may offer therapeutic strategies for diabetic complications affecting periodontal tissues.
