Non-receptor type, proline-rich protein tyrosine kinase 2 (Pyk2) is a possible therapeutic target for Kawasaki disease

• Project/Area Number: 26461616
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Nakamura Akihiro 京都府立医科大学, 医学(系)研究科(研究院), 博士研究員 (50313854)
• Co-Investigator(Kenkyū-buntansha): 浜岡 建城 京都府立医科大学, 医学(系)研究科(研究院), 教授 (60189602)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 川崎病 / 動物モデル / protein kinase / Pyk2 / 血管炎 / IP-10/CXCL10 / MIG/CXCL-9 / pyk2 / IP-10 / シグナル伝達 / カンジダ

Outline of Final Research Achievements

Kawasaki disease is a pediatric vasculitis whose etiology remains elusive. On the basis of experimental study with mouse model for KD, we report here that non-receptor type proline-rich tyrosine kinase 2 (pyk2) might be involved in the pathogenesis of KD. Pk2-KO mice were resistant to candida albicans extract (CAWS)-induced KD-like vasculitis. Two angiostatic chemokines, CXCL9 and 10 were increased in response to stimulation with CAWS. Considering that neo-angiogenesis is associated with KD-like murine vascuitis, sustained increase of these chemokines might be involved in resistance of pyk2 KO-mice to the vasculitis. Overall, pyk2 might be a promising therapeutic target for KD.

Research Products

• [Journal Article] Non-receptor type, proline-rich protein tyrosine kinase 2 (Pyk2) is a possible therapeutic target for Kawasaki disease. (2017)
  • Author(s): Suzuki C, Nakamura A, Miura N, Fukai K, Ohno N, Yahata T, Okamoto-Hamaoka A, Fujii M, Yoshioka A, Kuchitsu Y, Ikeda K, Hamaoka K
  • Journal Title: Clin Immunol Volume: 179 Pages: 17-24
  • DOI: 10.1016/j.clim.2017.01.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pyk2 aggravates hypoxia-induced pulmonary hypertension by activating HIF-1α. (2015)
  • Author(s): Fukai K et al.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 308 (8) Issue: 8 Pages: H951-H959
  • DOI: 10.1152/ajpheart.00770.2014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ピンポイント川崎病：原因をめぐる最近の議論 （総説） (2014)
  • Author(s): 中村明宏
  • Journal Title: 小児内科 Volume: 46 (6) Pages: 713-716
• [Journal Article] Involvement of mannose-binding lectin in the pathogenesis of kawasaki disease-like murine vasculitis (2014)
  • Author(s): Nakamura A, Okigaki M, Miura N, Suzuki C, Ohno N, Kametani F, Hamaoka K.
  • Journal Title: Clinical Immunology Volume: 153 Issue: 1 Pages: 64-72
  • DOI: 10.1016/j.clim.2014.03.019
  • Peer Reviewed
• [Presentation] 新生血管抑制をターゲットとした川崎病治療の可能性 (2016)
  • Author(s): 鈴木千夏、中村明宏、岡本亜希子、八幡倫代、吉岡綾子、朽津有紀、池田和幸、浜岡建城
  • Organizer: 第36回日本川崎病学会
  • Place of Presentation: ワークピア横浜(横浜市中区)
  • Year and Date: 2016-09-30
• [Presentation] 川崎病血管炎の IP-10 産生経路における Proline-rich tyrosine kinase 2 の 関与について (2015)
  • Author(s): 鈴木 千夏 、中村 明宏 、沖垣 光彦 、深井 邦剛 、大野 尚仁 、三浦 典子 、 八幡 倫代 、岡本 亜希子 、吉岡 綾子 、朽津 有紀 、池田 和幸 、濱岡 建城
  • Organizer: 第３５回日本川崎病学会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-10-09
• [Presentation] Involvement of Proline-rich tyrosine kinase 2 (Pyk2) in Kawasaki disease-like murine vasculitis (2015)
  • Author(s): Suzuki C, et al
  • Organizer: 49th Annual meeting of the association for pediatric and congenital cardiology
  • Place of Presentation: Prague
  • Year and Date: 2015-05-20 – 2015-05-23
• [Presentation] 川崎病発症機序における非受容体型 Proline-rich tyrosine kinase2 (Pyk2) の 関与について (2014)
  • Author(s): 鈴木千夏 他
  • Organizer: 第34回 日本川崎病学会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-31 – 2014-11-01