Regulation of blood-brain barrier function by membrane-type metalloproteinases

• Project/Area Number: 15K08424
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Yamaguchi University
• Principal Investigator: IKEDA EIJI 山口大学, 大学院医学系研究科, 教授 (30232177)
• Co-Investigator(Kenkyū-buntansha): 崔 丹 山口大学, 大学院医学系研究科, 講師 (40346549)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 血液脳関門 / claudin-5 / 低酸素 / 炎症 / 糖尿病網膜症 / メタロプロテアーゼ / 脳梗塞

Outline of Final Research Achievements

In various intractable neural diseases, the impairment of neural vascular barriers, including blood-brain barrier, occurs and accelerates their disease progression. As the candidates for target molecules to restore the neural vascular barrier, we have specified ADAM12, ADAM17 and basigin, all of which are expressed in endothelial cells. As for ADAM12 and ADAM17, they were shown to be involved predominantly in hypoxia-induced impairment of vascular barrier, and consequently to be unable to restore sufficiently the vascular barrier in neural diseases in which various stimuli, together with hypoxia, cause the vascular barrier disruption. On the other hand, it was demonstrated that basigin is involved in the impairment of vascular barrier as the common downstream molecule of various stimuli including hypoxia and multiple cytokines, and furthermore our study with animals indicated the potential of basigin as the target to establish the new effective treatment of intractable neural diseases.

Research Products

• [Journal Article] Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy. (2016)
  • Author(s): Arima, M., Cui, D., Kimura, T., Sonoda, K.H., Ishibashi, T., Matsuda, S., and Ikeda, E.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 38445-38445
  • DOI: 10.1038/srep38445
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 成体における神経系血管バリアーの病的破綻に対する治療戦略 (2017)
  • Author(s): 池田栄二
  • Organizer: 第21回日本神経麻酔集中治療学会
  • Invited
• [Presentation] ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function. (2016)
  • Author(s): Ikeda E, Cui D, Arima M
  • Organizer: Gordon Research Conference‘Barriers of the CNS’
  • Place of Presentation: Colby-Sawyer College, New London, NH, USA
  • Year and Date: 2016-06-19
  • Int'l Joint Research
• [Presentation] Therapeutic Targets for Hypoxia-induced Vasculopathy in Retina. (2015)
  • Author(s): Ikeda E
  • Organizer: The 27th International Conference of the Korean Society for Molecular and Cellular Biology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-09-21
  • Int'l Joint Research / Invited
• [Patent(Industrial Property Rights)] 神経系疾患治療剤 (2015)
  • Inventor(s): 池田栄二、有馬 充
  • Industrial Property Rights Holder: 山口大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-212817
  • Filing Date: 2015-10-29