Identification of phospholipase C for the treatment of nonalcoholic fatty liver disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19327
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kono Nozomu 東京大学, 大学院薬学系研究科(薬学部), 准教授 (50451852)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: ホスホリパーゼC / ホスファチジルイノシトール / 非アルコール性脂肪性肝疾患

Outline of Final Research Achievements

The degradation process of PI in Huh-7 cells was examined by d8 glycerol labeling, which revealed that PI degradation is species-specific and that the half-life of non-arachidonic acid-containing PI is shorter. PI degradation was not inhibited by the knockdown of PLC family members, PLCXD family members, and SMSr, which have been reported to have PI-PLC activity. On the other hand, in screening compounds that inhibit PI degradation, we found that an inhibitor of lipid phosphatases inhibits PI degradation.

Free Research Field

脂質生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果から得られた分子種特異的なPI分解ならびにPI-PLCの候補をさらに検討することで、非アルコール性脂肪性肝疾患の病態形成に関わるPI代謝およびその実行分子が明らかとなり、非アルコール性脂肪性肝疾患の新たな診断・治療戦略を提供することができる。