Analysis of liver cancer after suppression of angiogenesis and hepatic fibrosis regulated by vasohibins expression levels

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09386
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Furutani Yutaka 国立研究開発法人理化学研究所, 生命医科学研究センター, 上級研究員 (80392108)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: バソヒビン / SVBP / 肝線維化 / 血管新生

Outline of Final Research Achievements

Angiogenesis links hepatic fibrogenesis, and many reports show that angiogenesis concomitantly progresses with fibrogenesis. We assume that hepatic fibrosis could be suppressed by regulated expression levels of vasohibins, which mediates angiogenesis. To identify vasohibin-1,-2 expressing cells, we generated rabbit polyclonal antibodies against vasohibin-1, -2. Using these antibodies, transiently expressed vasohibin-1,-2 in Hela cells were specifically detected. Vasohibin-1,-2 are highly expressed in the brain. Thus, we performed imunohistochemical staining of the brain tissues prepared from wild-type and vasohibin-1,-2-deficient mice. We identified that vasohibin-1,-2 were expressed from neurons. But, we could not detect vasohibin-1,-2-expressing cells in the liver. To show vasohibin-2 function in hepatic fibrosis, we performed bile duct ligation. We could not find significant difference in markers for hepatic fibrosis between vasohibin-2-deficient and wild-type mice.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

肝癌により国内だけでも年間3万人が死亡し、100万人以上の患者がいる。これらの患者は一般的に肝線維化と肝硬変を経て肝癌へと進行していく、始めのステップである肝線維化を抑制することが重要となり、全世界的に肝線維化を抑制する薬剤の開発が進められている。肝線維化の分子機構を明らかにし、肝線維化の抑制から肝癌制御を目指すことは社会的に意義があり、迅速に取り組むべき研究課題である。また、バソヒビンはチューブリンの脱チロシン化を行うタンパク質であることが明らかとなり、細胞骨格と肝線維化・肝癌を結びつける重要なターゲット分子と考えられ特異的に認識するポリクローナル抗体の開発は学術的に意義がある。