Towards an integrated understandings of the inflammatory tissue remodeling in the pathogenesis of rheumatoid arthritis

• Project/Area Number: 24689056
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya City University (2016); Kyoto University (2012-2015)
• Principal Investigator: ASAGIRI Masataka 名古屋市立大学, 薬学研究科(研究院), 准教授 (20372435)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 関節リウマチ / 自己免疫 / 病理学 / 免疫学 / 炎症 / 組織破壊 / 組織再構築 / 骨代謝 / 自然免疫 / 組織変性

Outline of Final Research Achievements

Inflammatory bone destruction exceeds bone formation in the pathogenesis of rheumatoid arthritis (RA). In this study, we gained insights into the mechanism of RA bone destruction by elucidating a link in various organs in inflammation pathology. As a result, we clarified novel activation mechanisms of NFkB molecules (Nature Immunol 2012; Cell Reports 2012; Blood 2016); identified a subset of cells involved in inflammatory fibrosis (PNAS 2014); and elucidated the role of ion permeable channels and actin binding proteins in bone metabolism (Science Signaling 2016; Scientific Reports 2017).

Research Products

• [Journal Article] Inhibition of MMP-2-Mediated Mast Cell Invasion by NF-κB Inhibitor DHMEQ in Mast Cells (2015)
  • Author(s): Noma N, Asagiri M, Takeiri M, Ohmae S, Takemoto K, Iwaisako K, Minato N, Maeda-Yamamoto M, Simizu S, Umezawa K
  • Journal Title: Int Arch Allergy Immunol Volume: 166 Issue: 2 Pages: 84-90
  • DOI: 10.1159/000371419
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Migration of splenic lymphocytes promotes liver fibrosis through modification of T helper cytokine balance in mice (2015)
  • Author(s): Tanabe K, Taura K, Koyama Y, Yamamoto G, Nishio T, Okuda Y, Nakamura K, Toriguchi K, Takemoto K, Yamanaka K, Iwaisako K, Seo S, Asagiri M, Hatano E, Uemoto S.
  • Journal Title: Journal of Gastroenterology Volume: in press Issue: 10 Pages: 1054-1068
  • DOI: 10.1007/s00535-015-1054-3
  • Peer Reviewed
• [Journal Article] Strategies to Detect Hepatic Myofibroblasts in Liver Cirrhosis of Different Etiologies (2014)
  • Author(s): Iwaisako K, Taura K, Koyama Y, Takemoto K, Asagiri M.
  • Journal Title: Current Pathobiology Reports Volume: 2 Issue: 4 Pages: 209-215
  • DOI: 10.1007/s40139-014-0057-8
  • Peer Reviewed
• [Journal Article] Necrostatin-1 protects against reactive oxygen species (ROS)-induced hepatotoxicity in acetaminophen-induced acute liver failure. (2014)
  • Author(s): Takemoto K, Hatano E, Iwaisako K, Takeiri M, Noma N, Ohmae S, Toriguchi K, Tanabe K, Tanaka H, Seo S, Taura K, Machida K, Takeda N, Saji S, Uemoto S, Asagiri M.
  • Journal Title: FEBS Open Bio Volume: 4 Issue: 1 Pages: 777-787
  • DOI: 10.1016/j.fob.2014.08.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Origin of myofiblasts in the fibrotic liver in mice (2014)
  • Author(s): K.Iwaisako, C.Jiang, M.Zhang, M.Cong, T.J.Moore-Morris, T.J.Park, X.Liu, J.Xu, P.Wang, Y-H.Paik, F.Meng, M.Asagiri, L.A.Murray, A.F.Hofmann, T.Iida, C.K.Glass, D.A.Brenner, T.Kisseleva
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 111 Issue: 32
  • DOI: 10.1073/pnas.1400062111
  • Peer Reviewed
• [Journal Article] Generation of a mouse model with down-regulated U50 snoRNA (SNORD50) expression and its organ-specific phenotypic modulation (2013)
  • Author(s): Soeno Y, Fujita K, Kudo T, Asagiri M, Kakuta S, Taya Y, Shimazu Y, Sato K, Tanaka-Fujita R, Kubo S, Iwakura Y, Nakamura Y, Mori S, and Aoba T
  • Journal Title: PLoS ONE Volume: 8 Issue: 8 Pages: e72105-e72105
  • DOI: 10.1371/journal.pone.0072105
  • Peer Reviewed
• [Presentation] Involvement of regulated necrosis in the pathogenesis of drug-induced acute liver failure (2015)
  • Author(s): Takemoto K, Hatano E, Iwaisako K, Toriguchi K, Tanabe K, Taura K, Uemoto S, Asagiri M.
  • Organizer: SOT 2015 (54th Annual Meeting and ToxExpo of the Society of Toxicology)
  • Place of Presentation: San Diego Convention Center (San Diego, California, USA)
  • Year and Date: 2015-03-22 – 2015-03-26
• [Presentation] 薬剤性劇症肝炎の病態形成における制御性壊死の関与 (2014)
  • Author(s): 竹本研史，波多野悦朗，祝迫惠子，竹入雅敏，野間成人，鳥口寛，田邉和孝，瀬尾智，田浦康二朗，朝霧成挙，上本伸二
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館 (沖縄)
  • Year and Date: 2014-07-01 – 2014-07-04
• [Remarks] 京都大学医学研究科 次世代免疫制御を目指す創薬医学融合拠点 朝霧研究グループ
  • URL: http://www.ak.med.kyoto-u.ac.jp/group_research/asagiriG.html
• [Remarks] 京都大学医学研究科 次世代免疫制御を目指す創薬医学融合拠点 朝霧研究グループ
  • URL: http://www.ak.med.kyoto-u.ac.jp/group_research/asagiriG.html