Creation of new therapeutic strategies for vascular malformations by targeting the ubiquitin E3 complex

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10030
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Ehime University
• Principal Investigator: Nakaoka Hiroki 愛媛大学, 医学部附属病院, 准教授 (30172266)
• Co-Investigator(Kenkyū-buntansha): 東山 繁樹 愛媛大学, プロテオサイエンスセンター, 教授 (60202272)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 血管奇形 / 血管新生 / ユビキチンリガーゼ

Outline of Final Research Achievements

The dysregulation of angiogenesis, new vascular vessel formation, causes some vascular malformations. The disease leads to not only the decrease of patients’ quality of life but also the critical health issues such as heart failure. To date, pharmaceutics for vascular malformations is not well established because of the lack of molecular mechanisms underlying the formation of malformations. In this study, we found that a BTBP for the cullin-3/RING ubiquitin ligase complex highly expressed in endothelial cells of vascular malformations. We also screened compounds which inhibit the BTBP function using the AlphaScreen system. As a result, a set of compounds were identified as an inhibitor of the cullin-3/BTBP interaction.

Free Research Field

血管生物学、形成外科

Academic Significance and Societal Importance of the Research Achievements

血管奇形は異常／過剰な血管新生が原因となる疾患と考えられている。外見・容姿・機能面への影響に加え、重篤化すると心不全などの病態を引き起こすものも見られる。本研究で見出した血管奇形で発現するユビキチンリガーゼに対する阻害剤は今後新たな血管奇形の治療薬のシーズとして期待される。