Glomerular inflammation induced by innate immune reaction in residual glomerular cells and future therapeutic strategy for CKD
| Project/Area Number |
16K10055
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉田 秀見 弘前大学, 医学研究科, 講師 (40201008)
今泉 忠淳 弘前大学, 医学研究科, 教授 (90232602)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 培養ヒトメサンギウム細胞 / 培養ヒト糸球体上皮細胞 / Toll様受容体3 / 慢性腎臓病 / 糸球体腎炎 / 腎糸球体内皮細胞 / Toll様受容体３ / 抗マラリア薬 / インターロイキン６ / メサンギウム細胞 / Toll-like receptor 3 / Interferon-β / Cylindromatosis / CXCL1 / クロロキン / ISG / クラリスロマイシン / 小児腎・泌尿器学 / 自然免疫 |
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| Outline of Final Research Achievements |
We examined the Toll-like receptor (TLR) 3 signaling cascades triggered by polyinosinic-polycytidylic acid, a synthetic analogue of viral dsRNA, that elicites “pseudoviral” infection in cultured human mesangial cells (MCs) and glomerular endothelial cells (GECs), and found that TLR3/IFN-β activation and subsequent regional expressions of proinflammatory chemokines/cytokines in MCs and GECs may be a key trigger in the glomerular inflammatory cascades.
Although glomerular inflammation via innate immunity reportedly plays a pivotal role in the pathogenesis and progression of chronic kidney diseases (CKD), detailed signaling pathways via TLR3 activation in the residual glomerular cells have not always been studied so far.
Considering that TLR3 signaling is implicated in CKD pathogenesis, intervention in these signaling pathways may be a considerable therapeutic strategy for treating CKD in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病 (CKD)の病態形成には，感染症や内因性リガンドが惹起する自然免疫系 の活性化とこれに伴う慢性炎症の関与が知られているが，その分子病態学的詳細は不明の点が多い。ウイルス感染はCKDの発症機転や増悪因子となることが臨床観察で知られているが，その分子生物学的詳細に関しても不明な点が多い。
今回，培養ヒトメサンギウム細胞 (MCs)，培養ヒト糸球体内皮細胞 (GECs)でのウイルス dsRNAを認識する Toll様受容体3 (TLR3)を介する炎症経路群の詳細を検討，および腎生検組織での免疫染色から，TLR3を起点とする炎症病態の一部が明らかとなり，新規の治療法開発への足掛かりが得られた。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Cytosolic sensors of viral RNA are involved in the production of interleukin-6 via Toll-like receptor 3 signaling in human glomerular endothelial cells2019
Author(s)
Liu Q, Imaizumi T, Aizawa T, Hirono K, Kawaguchi S, Watanabe S, Tsugawa K, Matsumiya T, Seya K, Yoshida H, Tanaka H
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Journal Title
Kidney Blood Pressure Res
Volume: 44
Issue: 1
Pages: 62-71
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Toll-like receptor 3 signaling contributes to regional neutrophil recruitment in cultured human glomerular endothelial cells.2018
Author(s)
Liu Q, Imaizumi T, Kawaguchi S, Aizawa T, Matsumiya T, Watanabe S, Tsugawa K, Yoshida H, Tsuruga K, Joh K, Kijima H, Tanaka H
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Journal Title
Nephron
Volume: 139
Issue: 4
Pages: 349-358
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cylindromatosis (CYLD), a deubiquitinase, attenuates inflammatory signaling pathways by activating Toll-like receptor 3 in human mesangial cells.2017
Author(s)
Imaizumi T, Hayakari R, Watanabe S, Aizawa T, Matsumiya T, Yoshida H, Tsuruga K, Kawaguch S, Tanaka H
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Journal Title
Kidney and Blood Pressure Research
Volume: 42
Issue: 5
Pages: 942-950
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Interferon (IFN)-induced protein 35 (IFI35), a type I interferon-dependent transcript, upregulates inflammatory signaling pathways by activating Toll-like receptor 3 in human mesangial cells.2016
Author(s)
Imaizumi T, Yano C, Numata A, Tsugawa K, Hayakari R, Matsumiya T, Yoshida H, Watanabe S, Tsuruga K, Kawaguchi S, Murakami M, Tanaka H.
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Journal Title
Kidney and Blood Pressure Research
Volume: 41
Issue: 5
Pages: 635-642
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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