Analysis of the molecular mechanism of hepatic fibrosis initiating from lipid peroxidation of lipid-soluble signaling molecules

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08721
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokai University
• Principal Investigator: TAKEKOSHI Susumu 東海大学, 医学部, 教授 (70216878)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: lipid peroxidation / lipid peroxide / protein kinase c / diacylglycerol / liver fibrosis / oxidative stress / ｍass spectrometry / hepatic stellate cell

Outline of Final Research Achievements

We analyzed the molecular mechanism of liver fibrosis starting from peroxidized DAG. Peroxidized DAG was significantly increased in mouse liver tissue in which liver fibrosis was induced by carbon tetrachloride administration. In addition, the administration of Ebselen, which has the ability to reduce and eliminate peroxidized DAG, suppressed the increase in peroxidized DAG and improved the liver fibrosis. When peroxidized DAG was applied to primary-cultured cells of mouse hepatic stellate cells, the hepatic stellate cells were activated and changed into myofibroblast-like cells. From the above results, it was clarified that peroxidized DAG produced by oxidative stress acts as a key molecule in liver fibrosis.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、これまで漠然とした傷害作用として捉えられてきた酸化ストレス傷害を、特定の機能性脂質分子（DAG）の過酸化による特定のPKCアイソザイムの活性化と情報伝達異常、さらにはこれに対応する酸化ストレスシグナル抑制分子による制御応答といった分子レベルでの理解を可能とし、本研究で対象としている肝線維化疾患ばかりでなく、酸化ストレスが関与するとされる、アルツハイマー病、パーキンソン病などの神経変性疾患、動脈硬化症、虚血―再疎通疾患などの種々の疾患の病因の厳密な追求、解明を行う際の重要な拠点となるものと思われる。