MicroRNA-126 Regulates Inflammatory Cytokine Secretion in Human Gingival Fibroblasts Under High Glucose via Targeting Tumor Necrosis Factor Receptor Associated Factor 6

• Autores: Yi Wu, Li-Ting Song, Jia-Shan Li, Dong-Wang Zhu, Shao-Yun Jiang, Jia-Yin Deng
• Localización: Journal of periodontology, ISSN 0022-3492, Vol. 88, Nº. 11, 2017, págs. 179-187
• Idioma: inglés
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• Resumen

  • Background: MicroRNAs (miRs) play a crucial role in inflammatory diseases, including periodontitis. Meanwhile, miRs act as biomarkers for predicting diabetes mellitus (DM). However, the regulatory mechanism of miR-126 on development of periodontitis in patients with DM still remains unclear.

    Methods: Human gingival fibroblasts were cultured with low (5.5 mmol/L), medium (15 mmol/L), and high (25 mmol/L) glucose, respectively. Expressions of miR-126, tumor necrosis factor (TNF) receptor associated factor (TRAF) 6, and related cytokines were analyzed by real-time polymerase chain reaction (PCR). After transfection with miR- 126 mimic, PCR and western blot were performed to detect level of TRAF6, and luciferase reporter assay confirmed if TRAF6 is the direct target of miR-126. Production of cytokines was measured using enzyme-linked immunosorbent assay.

    Results: Increased glucose significantly suppressed miR- 126 expression in human gingival fibroblasts (P <0.05).

    Also, high glucose increased TRAF6, interleukin (IL)-6, TNFa, and chemical chemokine ligand (CCL) 2 levels, whereas it decreased IL-10 level. MiR-126 mimic significantly decreased TRAF6 mRNA and protein levels under high glucose (P <0.05). Also, miR-126 directly targeted TRAF6 through binding to its 39 untranslated region in human gingival fibroblasts.

    Overexpression of miR-126 significantly abrogated high glucose–induced secretion of proinflammatory cytokines such as IL-6, TNF-a, and CCL2 and promoted production of IL-10.

    Conclusion: These data suggest that miR-126 inhibits in- flammation of human gingival fibroblasts under high glucose through targeting TRAF6, which may be a potential therapeutic target for periodontitis concomitant with DM. J Periodontol 2017;88:e179-e187