Development of therapeutic strategies for RA targeting TNF-α-inducible RNA receptors in cytoplasm

2012 Fiscal Year Final Research Report

• Project/Area Number: 21591259
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• 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): ISHIGURO You 弘前大学, 医学(系)研究科(研究院), 研究員 (10312498) ; ISHIBASHI Yasuyuki 弘前大学, 医学(系)研究科(研究院), 教授 (80292142) ; YOSHIDA Hidemi 弘前大学, 医学(系)研究科(研究院), 講師 (40201008) ; MATSUMIYA Tomoho 弘前大学, 医学(系)研究科(研究院), 助教 (30344592) ; SATOH Kei 弘前大学, 事務局, 学長 (20125438)
• Project Period (FY): 2009 – 2012
• Keywords: リウマチ / ループス腎炎 / RIG-I / MDA5 / 細胞質RNA受容体 / 慢性炎症

Research Abstract

Retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are TNF-α-inducible RNA receptors in cytoplasm. The expression of RIG-I and MDA5 are induced by viral infection, and are increased in chronic inflammatory diseases such as rheumatoid arthritis and lupus nephritis which can be triggered or worsened by viral infections. Knockdown of RIG-I and/or MDA5 resulted in the induction of inflammatory cytokines，and RIG-I and MDA5 can be molecules which can be new therapeutic targets.

Research Products

• [Journal Article] Foreign RNA induces the degradation of mitochondrial antiviral signaling protein (MAVS)the role of intracellular antiviral factors. (2012)
  • Author(s): Xing F, Matsumiya T, Onomoto K, Hayakari R, Imaizumi T, Yoshida H, Yoneyama M, Fijita T, Satoh K
  • Journal Title: PLoS One Volume: 7(9) Pages: e45136
  • DOI: doi:10.1371/journal.pone.0045136.
• [Journal Article] Double-stranded RNA induces biphasic STAT1 phosphorylation by both type I IFN-dependent and type I IFN-independent pathways (2012)
  • Author(s): Dempoya J, Matsumiya T, Imaizumi T, Hayakari R, Xing F, Yoshida H, Okumura K, Satoh K
  • Journal Title: J Virol Volume: 86(23) Pages: 12760-12769
  • DOI: doi:10.1128/JVI.01881-12.
• [Journal Article] Melanoma differentiation-associated gene 5 regulates the expression of a chemokine CXCL10 in human mesangial cells (2012)
  • Author(s): Imaizumi T, Aizawa-Yashiro T, Tsuruga K, Tanaka H, Matsumiya T, Yoshida H, Tatsuta T, Xing F, Hayakari R, Satoh K
  • Journal Title: implications for chronic inflammatory renal diseases. Tohoku J Exp Med Volume: 228 Pages: 17-26
  • DOI: doi:10.1620/tjem.228.17.
• [Journal Article] Fukuda S : Expression of melanoma differentiation associated gene 5 (MDA5) is increased in human gastric mucosa infected with Helicobacter pyroli (2012)
  • Author(s): Tatsuta T, Imaizumi T, Shimoyama T,Sawaya M, Tanji K, Matsumiya T, Yoshida H, Satoh K
  • Journal Title: J Clin Pathol Volume: 65 Pages: 839-843
  • DOI: doi:10.1136/jclinpath-2011-200590.
• [Journal Article] Sawamura D. : Characterization of retinoic acid-inducible gene-I (RIG-I) expression corresponding to viral infection and UVB in human keratinocytes (2012)
  • Author(s): Kimura K, Matsuzaki Y, Nishikawa Y, Kitamura H, Akasaka E, Rokunohe D, Nakano H, Imaizumi T, Satoh K
  • Journal Title: J Dermatol Sci 2012 Volume: 66(1) Pages: 66-70
  • DOI: doi:10.1016/j.jdermsci.2012.02.006.
• [Journal Article] Imbalance towards Th1 pathway predominance in purpura neohritis with proteinuria. (2011)
  • Author(s): Tsuruga K, Watanabe S, Oki E, Aizawa-Yashiro T, Yoshida H, Imaizumi T, Ito E, Tanaka H
  • Journal Title: Pediat Nephrol Volume: 26 Pages: 2253-2258
  • DOI: doi:10.1007/s00467-011-1996-5.
• [Journal Article] Type-III interferon, not type-I, is the predominant interferon induced by respiratory viruses in nasal epithelial cells. (2011)
  • Author(s): Okabayashi T, Kojima T, Masaki T, Yokota SI, Imaizumi T, Tsutsumi H, Himi T, Fujii N, Sawada N
  • Journal Title: Virus Res Volume: 160(1-2) Pages: 360-366
  • DOI: doi:10.1016/j.virusres.2011.07.011
• [Journal Article] Polyinosinic-polycytidylic acid induces the expression of interferon-stimulated gene 20 in mesangial cells (2011)
  • Author(s): Imaizumi T, Tanaka H, Mechti N, Matsumiya T, Yoshida H, Sato F, Aizawa-Yashiro T, Tsuruga K, Hayakari R, Satoh K
  • Journal Title: Nephron Exp Nephrol Volume: 119(2) Pages: e40-e48
  • DOI: doi:10.1159/000328923.
• [Journal Article] Basic-helix-loop-helix transcription factor DEC2 constitutes negative feedback loop in IFN-g-mediated inflammatory responses in human mesangial cells. (2011)
  • Author(s): Imaizumi T, Yoshida T, Sato F, Tanaka H, Yashiro-Aizawa K, Hayakari R, Kijima H, Matsumiya T, Tsuruga H, Satoh K
  • Journal Title: Immunol Lett Volume: 136 Pages: 37-43
  • DOI: doi:10.1016/j.imlet.2010.11.009.
• [Journal Article] Retinoic acid-inducible gene-I is induced by double-stranded RNA and regulates the expression of CCL5 in human mesangial cells (2010)
  • Author(s): Imaizumi T, Tanaka H, Matsumiya T, Yoshida H, Tanji K, Tsuruga K, Oki E, Yashiro T, Ito E, Satoh K
  • Journal Title: Nephrol Dial Transplant Volume: 25 Pages: 3534-3539
  • DOI: doi:10.1093/ndt/gfq270.
• [Journal Article] IFN-γ and TNF-α synergistically induce microRNA-155 which regulates TAB2/IP-10 expression in human mesangial cells (2010)
  • Author(s): Imaizumi T, Tanaka H, Tajima A, Yokono Y, Matsumiya T, Yoshida H, Tsuruga K, Aizawa-Yashiro T, Hayakari R, Inoue I, Ito E, Satoh K
  • Journal Title: Am J Nephrol Volume: 32 Pages: 462-468
  • DOI: doi:10.1159/000321365.
• [Journal Article] Potential Th1/Th2 predominance in children with newly diagnosed IgA nephropathy (2010)
  • Author(s): Tsuruga K, Oki E, Aizawa-Yashiro T, Yoshida H, Imaizumi T, Tanaka H
  • Journal Title: Acta Paediatr Volume: 99 Pages: 1584-1586
  • DOI: doi:10.1111/j.1651-2227.2010.01881.x.
• [Journal Article] Retinoic acid-inducible gene-I (RIG-I) is induced by IFN-γ in human mesangial cells in culture (2010)
  • Author(s): Imaizumi T, Tanaka H, Tajama A, Tsuruga K, Oki E, Sashinami H, Matsumiya T, Yoshida H, Inoue I, Ito E
  • Journal Title: possible involvement of RIG-I in the inflammation in lupus nephritis. Lupus Volume: 19(6) Pages: 830-836
  • DOI: doi:10.1177/0961203309360540.
• [Journal Article] Characterization of synergistic induction of CX3CL1/Fractalkine by TNF-α and IFN-γ in vascular endothelial cells (2010)
  • Author(s): Matsumiya T, Ota K, Imaizumi T, Yoshida H, Kimura H, Satoh K
  • Journal Title: an essential role for TNF-a in post-transcriptional regulation of CX3CL1. J Immunol Volume: 184 Pages: 4205-4214
  • DOI: doi:10.4049/jimmunol.0903212.
• [Journal Article] Edaravone improves the expression of nerve growth factor in human astrocytes subjected to hypoxia/reoxygenation (2010)
  • Author(s): Yoshida H, Metoki N, Ishikawa A, Imaizumi T, Matsumiya T, Tanji K, Ota K, Ohyama C, Satoh K
  • Journal Title: Neurosci Res Volume: 66(3) Pages: 284-289
  • DOI: doi:10.1016/j.neures.2009.11.011.
• [Journal Article] The viral RNA recognition sensor RIG-I is degraded during encephalomyocarditis virus (EMCV) (2009)
  • Author(s): Papon L, Oteiza A, Imaizumi T, Kato H, Brocchi E, Lawson TG, Akira S, Mechti N
  • Journal Title: infection. Virology Volume: 393(2) Pages: 311-318
  • DOI: doi:10.1016/j.virol.2009.08.009.
• [Journal Article] Metformin restores impaired HDL-mediated cholesterol efflux due to glycation (2009)
  • Author(s): Matsuki K, Tamasawa N, Yamashita M, Tanabe J, Murakami H, Imaiuzmi T, Satoh K, Suda T
  • Journal Title: Atherosclerosis Volume: 206(2) Pages: 434-438
  • DOI: doi:10.1016/j.atherosclerosis.2009.03.00 3.
• [Journal Article] Retinoic acid-inducible gene-I is constitutively expressed and involved in IFN-γ-stimulated CXCL9-11 production in intestinal epithelial cells (2009)
  • Author(s): Kawaguchi S, Ishiguro Y, Imaizumi T, Mori F, Matsumiya T, Yoshida H, Ota K, Sakuraba H, Yamagata K, Sato Y, Tanji K, Haga T, Wakabayashi K, Fukuda S, Satoh K
  • Journal Title: Immunol Lett Volume: 123(1) Pages: 9-13
  • DOI: doi:10.1016/j.imlet.2009.01.008.
• [Journal Article] The levels of retinoic acid-inducible gene-I are regulated by heat shock protein 90-α (2009)
  • Author(s): Matsumiya T, Imaizumi T, Yoshida H,Satoh K, Topham MK, Stafforini DM
  • Journal Title: J Immunol Volume: 182(5) Pages: 2717-2725
  • DOI: doi:10.4049/jimmunol.0802933.
• [Journal Article] Tumor-necrosis factor-α induces retinoic acid-inducible gene-I in rheumatoid fibroblast-like synoviocytes (2009)
  • Author(s): Imaizumi T, Matsumiya T, Yoshida H, Naraoka T, Uesato R, Ishibashi Y, Ota K, Toh S, Fukuda S, Satoh K
  • Journal Title: Immunol Lett Volume: 122 Pages: 89-93
  • DOI: doi:10.1016/j.imlet.2008.12.005.
• [Presentation] 2本鎖RNAによるmitochondrial antiviral signaling protein 発現調節の検討 (2012)
  • Author(s): Fei XING
  • Organizer: 第96回弘前医学会総会
  • Place of Presentation: 黒石市
  • Year and Date: 2012-06-16
• [Presentation] Helicobacter pylori感染と胃粘膜におけるmelanoma differentiation associated gene 5 (MDA5)の発現 (2012)
  • Author(s): 立田哲也
  • Organizer: 第109回日本内科学会講演会
  • Place of Presentation: 京都市
  • Year and Date: 2012-04-13
• [Presentation] Retinoic acid-inducible gene-I誘導は早期反応相においてインターフェロン非依存的な経路を有する (2012)
  • Author(s): 傅法谷純一
  • Organizer: 第149回弘前医学会例会
  • Place of Presentation: 弘前市
  • Year and Date: 2012-01-27
• [Presentation] Helicobacter pylori感染と自然免疫 (2011)
  • Author(s): 立田哲也
  • Organizer: 第95回弘前医学会総会
  • Place of Presentation: 十和田市
  • Year and Date: 2011-06-18
• [Presentation] ウイルスセンサーRIG-Iの転写調節機構に関する研究 (2011)
  • Author(s): 早狩亮
  • Organizer: 第148回弘前医学会例会
  • Place of Presentation: 弘前市
  • Year and Date: 2011-01-28