Does platelet-type 12-lipoxygenase play any role in the development of fibrosis in NASH?

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K11515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• 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): 2020-04-01 – 2024-03-31
• Keywords: 血小板型12-リポキシゲナーゼ / 肝星細胞

Outline of Final Research Achievements

We established the human hepatic stellate TWNT-1 cells stably expressing human platelet-type 12-lipoxygenase. The expression levels of type I collagen mRNA were decreased in the human platelet-type 12-lipoxygenase-expressing TWNT-1 cells as compared with mock cells or wild-type cells. The level of liver fibrosis in NASH model mice prepared by feeding methionine-choline deficient diet for 8 weeks using platelet-type 12-lipoxygenase-deficient mice was more progressed as compared with that in the model mice developed using wild-type mice. We found genes that suppressed the expression level of type I collagen mRNA in human hepatic stellate TWNT-1 cells by overexpression of platelet-type 12-lipoxygenase.

Free Research Field

脂質生化学

Academic Significance and Societal Importance of the Research Achievements

MCDマウスを用いて、肝線維化の進展過程における肝星細胞の活性化と筋線維芽細胞への分化によるコラーゲン産生増加の過程において、血小板型12-リポキシゲナーゼの果たす役割の一端が解明された。今後、血小板型12-リポキシゲナーゼ生成物の何が線維化の抑制に関わるか明らかになれば、NASHを含む多くの慢性炎症性肝疾患の進展における肝線維化進行抑制のメカニスムの解明につながるのみならず、新たな治療法の発見につながる可能性がある。