| Project/Area Number |
20K18512
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57030:Conservative dentistry-related
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| Research Institution | Kyushu University |
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Principal Investigator |
Sano Tomomi 九州大学, 歯学研究院, 助教 (50782075)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | microRNA / 炎症 / マクロファージ / 肥満 / 脂肪組織炎症 / 慢性炎症 / 歯周炎 / インスリン抵抗性 |
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| Outline of Research at the Start |
本研究は、脂肪組織において炎症性遺伝子 (mRNA) 発現を制御するmiRNAを特定し、そのmiRNAを封入・保護したカプセルには抗炎症効果があることを検証し、肥満およびインスリン抵抗性、ならびにそれらを合併した歯周病への治療効果を実証することを目的とする。
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| 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.
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| 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。
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