Elucidation of the mechanism of anoikis induction by vitamin E-analogous compound and application to the pharmacotherapy for hepatic cirrhosis.

2015 Fiscal Year Final Research Report

• Project/Area Number: 24614003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrated Nutrition Science
• Research Institution: Akita University
• Principal Investigator: Yamaguchi Noriko 秋田大学, 医学(系)研究科(研究院), 准教授 (90251553)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Kiwamu 秋田大学, 大学院医学系研究科, 助教 (90400481) ; MEZAKI Yoshihiro 東京慈恵会医科大学, 医学部, 講師 (40431621)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 肝硬変 / 肝臓星細胞 / アノイキス / コラーゲン / MMP

Outline of Final Research Achievements

In pathological conditions, hepatic stellate cells (HSCs) are activated and play crucial roles in liver fibrosis and hepatic cirrhosis. We reported that tocol, a vitamin E-analogous compound, strongly inhibited the proliferation and promoted the apoptosis of activated HSCs. Significant cell detachment was observed in tocol-treated HSCs, and apoptosis was mainly observed in floating cells. Therefore, it is considered that tocol induced anoikis, a specific type of apoptosis. In this study, the fragmentation of focal adhesion kinase was observed in tocol-treated cells, and protease inhibitors attenuated the cell detachment. Gene expression variation analysis showed that tocol elicited decreased expression of fibrillar collagens and increased expression of matrix metalloproteinases, which degrade extracellular matrix proteins.

Free Research Field

生化学、細胞生物学