Mechanisms for the regulation of vascular homeostasis by functional lipid molecules

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390051
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Kanazawa University
• Principal Investigator: TAKUWA Yoh 金沢大学, 医学系, 教授 (60171592)
• Co-Investigator(Renkei-kenkyūsha): OKAMOTO Yasuo 金沢大学, 医学系, 准教授 (80293877) ; YOSHIOKA Kazuaki 金沢大学, 医学系, 助教 (80333368) ; TAKUWA Noriko 石川県立看護大学, 看護学部, 教授 (70150290)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 脂質メディエーター / スフィンゴシンー１－リン酸 / イノシトールリン脂質 / PI3-キナーゼ / シグナル伝達 / 血管新生 / 血管障壁 / 血管医学

Outline of Final Research Achievements

We studied the mechanisms by which sphingosine-1-phosphate receptor S1P2 and phosphatidylinositol 3-kinase (PI3K) class II α-isoform (PI3K-C2α). S1P2 in the vascular endothelium protected the vasculature from acute disruption of vascular barrier integrity induced by anaphylactic mediators and lipopolysaccharide. This effect was mediated by S1P2-mediated inhibition of Akt and eNOS. S1P2 decreased the generation of nitric oxide (NO) by eNOS, resulting in inhibition of NO-mediated disruption of adherens junctions. Genetic deletion of PI3K-C2α impaired developmental and pathological angiogenesis. PI3K-C2α was necessary for VE-cadherin transport to the cell-cell junction, VEGF receptor endocytosis and endosomal receptor signaling, through which PI3K-C2α served an essential role in angiogenesis.

Free Research Field

血管医学、病態医化学、生理学、細胞生物学