Novel anti-sepsis strategy targeting the endothelial cell-specific receptor Robo4

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293014
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: Okada Yoshiaki 大阪大学, 薬学研究科(研究院), 准教授 (50444500)
• Co-Investigator(Kenkyū-buntansha): 土井 健史 大阪大学, 薬学研究科(研究院), 教授 (00211409)
• Co-Investigator(Renkei-kenkyūsha): FUJIO Yasushi 大阪大学, 薬学研究科, 教授 (20359839) ; KURODA Etsushi 大阪大学, 免疫学フロンティアセンター, 特任准教授 (10299604)
• Research Collaborator: Aird William Harvard Medical School, 教授
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Robo4 / 敗血症 / 血管内皮細胞 / 炎症 / 単球 / インターロイキン6 / 治療薬 / 低分子化合物

Outline of Final Research Achievements

The goal of our study is to develop a new drug to treat sepsis. Although antibiotics and steroids have been used for the treatment of sepsis, their effects are limited. To development new anti-sepsis drugs targeting vascular blood vessels, we focused on Robo4 that is a transmembrane receptor specifically expressed in endothelial cells. In this study we demonstrated that Robo4 downregulation suppresses IL-6 production not only from endothelial cells but also from monocytes though a crosstalk with GM-CSF, suggesting a new anti-sepsis strategy using molecules that inhibit Robo4 expression. To this end, we established a screening system for small molecules that suppress Robo4 expression.

Free Research Field

血管生物学