Development of a novel anti-inflammatory drug targeting miRNAs common to obesity and periodontitis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18512
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Sano Tomomi 九州大学, 歯学研究院, 助教 (50782075)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: microRNA / 炎症 / マクロファージ

Outline of Final Research Achievements

We identified miR-582-5p that was significantly downregulated in inflamed murine adipose tissues and RAW264.7 cells. SKP1, a core component of an E3 ubiquitin ligase that regulates the NF-κB pathway, was proposed as a biological target of miR-582-5p by using TargetScan. The binding of miR-582-5p to a 3'-untranslated region site on Skp1 was confirmed using a dual-luciferase reporter assay; in addition, transfection with a miR-582-5p mimic suppressed SKP1 expression in RAW264.7 cells. Importantly, exogenous miR-582-5p attenuated the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 through suppressing the degradation of the NF-κB inhibitor alpha, followed by the nuclear translocation of NF-κB. Therefore, exogenously applied miR-582-5p can attenuate the NF-κB signaling pathway via targeting Skp1; this provides a prospective therapeutic strategy for treating inflammatory and immune diseases.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

脂肪組織炎症状態で発現が変動し、抗炎症作用のあるmiRNAを同定した。また、Skp1を直接のターゲットとすること、さらにはSkp1発現が抑制することによるmiR-582-5pの抗炎症メカニズムも明らかにした本研究は、動脈硬化症や高血圧症、LDLコレステロール値の上昇といった病態を示す日本人に多い軽度肥満型のメタボリックシンドロームに対する新たな治療戦略の構築において多大な貢献をもたらすと考えている。