Study aiming for the development of NASH prevention focusing on lipoxygenase

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08916
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Okayama Prefectural University
• Principal Investigator: Takahashi Yoshitaka 岡山県立大学, 保健福祉学部, 教授 (10236333)
• Co-Investigator(Kenkyū-buntansha): 川上 祐生 岡山県立大学, 保健福祉学部, 准教授 (30453202)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 12-リポキシゲナーゼ / 非アルコール性脂肪性肝炎

Outline of Final Research Achievements

The catalytic activity of 12S-lipoxygenase was clearly detectable in liver cytosol of NASH model mice prepared by feeding a methionine and choline-deficient (MCD) diet. The product profile, substrate specificity and immunogenicity indicated that the enzyme was the platelet-type isoform. The expression levels of mRNA and protein of platelet-type 12S-lipoxygenase were significantly increased as compared with those of normal chow-fed mice. Immunohistochemical analysis showed that platelet-type 12S-lipoxygenase colocalized with alpha-smooth muscle actin as well as vitamin A in the cells distributing along liver sinusoids. These results indicate that the expression level of platelet-type 12S-lipoxygenase in hepatic stellate cells was increased during the cell activation in MCD diet-fed mice,.

Free Research Field

応用薬理学

Academic Significance and Societal Importance of the Research Achievements

慢性炎症肝において線維化の主役として働く肝星細胞に血小板型12-リポキシゲナーゼの局在が証明され、線維化の進行に伴って本酵素が誘導される可能性が示唆されたことは、本酵素が慢性炎症性肝疾患における線維化の進行において何らかの重要な役割を果たすことを強く示唆しており、今後この役割が解明されれば、慢性炎症性肝疾患の予後の決定因子の一つである線維化の予防につながると考えられ、学術的社会的意義は大きい。