MiR-146a Is Mutually Regulated by High Glucose-Induced Oxidative Stress in Human Periodontal Ligament Cells

• Published in: International journal of molecular sciences Vol. 25; no. 19; p. 10702
• Main Authors: Fumimoto, Chihiro, Yamauchi, Nobuhiro, Minagawa, Emika, Umeda, Makoto
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2024; MDPI
• Subjects: Cell growth; Cell Proliferation - drug effects; Cells, Cultured; Complications and side effects; Cysteine; Cytokines; Cytokines - metabolism; Development and progression; Dextrose; Diabetes; Enzyme-linked immunosorbent assay; Fibroblasts; Gene expression; Gene Expression Regulation - drug effects; Genetic aspects; Glucose; Glucose - metabolism; Glucose - pharmacology; Gum disease; Health aspects; high glucose; hPDLCs; Humans; Hyperglycemia; Inflammation; Interleukin-1 Receptor-Associated Kinases - genetics; Interleukin-1 Receptor-Associated Kinases - metabolism; Interleukins; Intracellular Signaling Peptides and Proteins; Investigations; Kinases; Ligaments; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-146a; Oxidative stress; Oxidative Stress - drug effects; Periodontal disease; Periodontal Ligament - cytology; Periodontal Ligament - metabolism; Physiological aspects; Proteins; Reactive Oxygen Species - metabolism; Risk factors; ROS; Scientific equipment and supplies industry; TNF Receptor-Associated Factor 6 - genetics; TNF Receptor-Associated Factor 6 - metabolism; Type 2 diabetes; Wound healing; United States; Japan; miR-146a; high glucose; ROS; hPDLCs
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251910702

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.