Role of mesangial RNA recognition receptors in innate immunity and chronic renal diseases

• Project/Area Number: 25461204
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Hirosaki University
• Principal Investigator: Imaizumi Tadaatsu 弘前大学, 医学(系)研究科(研究院), 教授 (90232602)
• Co-Investigator(Kenkyū-buntansha): TANAKA Hiroshi 弘前大学, 教育学部, 教授 (50271820) ; SHIMADA Michiko 弘前大学, 医学部附属病院, 講師 (40463765)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ISG / IFN / RIG-I / TLR3 / CCL5 / TLR / innate immunity / メサンギウム細胞 / IFN-beta

Outline of Final Research Achievements

Innate immune reactions are important in not only in host defense but also inflammatory renal diseases. Recognition of exogenous or endogenously released RNA by Toll-like receptor 3 (TLR3) induces the expression of interferon (IFN)-beta and activates innate immune reaction and downstream inflammatory reactions in mesangial cells. IFN-beta induces hundreds of IFN-sinducible genes (ISGs). We examined the role of several ISGs in TLR3 / IFN-beta / phosphorylated STAT1 / retinoic acid-inducible gene-I (RIG-I) / CCL5 axis in cultured human mesangial cells, and found that ISG56, ISG54 and ISG60 positively regulates this axis, while ISG15 negatively regulates this axis. These results suggest that TLR3-mediated innate immune reactions are tightly regulated by various ISGs and dysregulation of these ISGs may cause the onset and/or worsening of chronic renal diseases.

Research Products

• [Journal Article] Interferon-Dependent Transcript, Is Involved in a Negative Feedback Loop in Innate Immune Reactions in Human Mesangial Cells. (2016)
  • Author(s): Imaizumi T, Shimada T, Matsumiya T, Yoshida H, Watanabe S, Tsuruga K, Kawaguchi S, Murakami M, Joh K, Tanaka H.
  • Journal Title: Nephron Volume: 132 Issue: 2 Pages: 144-152
  • DOI: 10.1159/000443934
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells. (2015)
  • Author(s): Imaizumi T, Aizawa T, Segawa C, Shimada M, Tsuruga K, Kawaguchi S, Matsumiya T, Yoshida H, Joh K, Tanaka H:
  • Journal Title: Clinical and Experimental Nephrology Volume: 19 Issue: 5 Pages: 761-770
  • DOI: 10.1007/s10157-014-1060-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expressions of mRNA for innate immunity-associated functional molecules in urinary sediment in immunoglobulin A nephropathy. (2015)
  • Author(s): Tsuruga K, Aizawa T, Watanabe S, Tsugawa K, Yoshida H, Imaizumi T, Ito E, Tanaka H.
  • Journal Title: Nephrology (Carlton) Volume: 20 Issue: 12 Pages: 916-921
  • DOI: 10.1111/nep.12533
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tumor necrosis factor-α synergistically enhances polyinosinic-polycytidylic acid-induced toll-like receptor 3 signaling in cultured normal human mesangial cells: possible involvement in the pathogenesis of lupus nephritis (2014)
  • Author(s): Imaizumi T, Aizawa T, Hayakari R, Xing F, Meng P, Tsuruga K, Matsumiya T, Yoshida H, Wang L, Tatsuta T, Tanaka H
  • Journal Title: Clin Exp Nephrol Volume: (online ahead of print) Issue: 1 Pages: 75-81
  • DOI: 10.1007/s10157-014-0956-3
  • Peer Reviewed / Open Access
• [Journal Article] Interaction between interferon-stimulated gene 56 and melanoma differentiation-associated gene 5 in toll-like receptor 3 signaling in normal human mesangial cells (2013)
  • Author(s): Imaizumi T, Aizawa-Yashiro T, Matsumiya T, Yoshida H, Watanabe S, Tsuruga K, Tatsuta T, Xing F, Hayakari R, Meng P, Tanaka H.
  • Journal Title: Am J Nephrol Volume: 37 Issue: 2 Pages: 118-125
  • DOI: 10.1159/000346415
  • Peer Reviewed
• [Journal Article] TLR4 signaling induces retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 in mesangial cells. (2013)
  • Author(s): Imaizumi T, Aizawa-Yashiro T, Watanabe S, Matsumiya T, Yoshida H, Tatsuta T, Xing F, Meng P, Hayakari R, Tsuruga K, Tanaka H.
  • Journal Title: J Nephrol Volume: 26 Issue: 5 Pages: 886-893
  • DOI: 10.5301/jn.5000254
  • Peer Reviewed
• [Journal Article] Glomerular expression of myxovirus resistance protein 1 (Mx1) in human mesangial cells: possible activation of innate immunity in the pathogenesis of lupus nephritis. (2013)
  • Author(s): Watanabe S, Imaizumi T, Tsuruga K, Aizawa T, Ito T, Matsumiya T, Yoshida H, Joh K, Ito E, Tanaka H:
  • Journal Title: Nephrology Volume: 18 Pages: 833-837
  • Peer Reviewed
• [Journal Article] Urinary fractalkine and monocyte chemoattractant protein-1 as possible predictors of disease activity of childhood glomerulonephritis. (2013)
  • Author(s): Aizawa T, Imaizumi T, Tsuruga K, Watanabe S, Yoshida H, Kumagai N, Ito E, Tanaka H.
  • Journal Title: Tohoku J Exp Med Volume: 231 Pages: 265-270
  • NAID: 130004822389
  • Peer Reviewed
• [Presentation] 慢性炎症、動脈硬化、自然免疫、そして腎疾患 (2015)
  • Author(s): 今泉忠淳
  • Organizer: 第25回東北小児腎臓病研究会
  • Place of Presentation: 弘前市
  • Year and Date: 2015-03-14
  • Invited
• [Presentation] 腎糸球体疾患の非侵襲的診断法開発の試み：尿中 MCP-1、fractalkine は病勢を反映するか？
  • Author(s): 相澤知美、伊東竜也、渡邉祥二郎、敦賀和志、今泉忠淳、田中 完、伊藤悦朗
  • Organizer: 第75回腎懇話会
  • Place of Presentation: 弘前市