Role of tissue fibrinolytic factors in NASH liver fibrosis and intrahepatic macrophage activation

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10666
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Iwaki Takayuki 浜松医科大学, 医学部, 准教授 (70509463)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: LDL / apoB100 / Macrophage / Foam cell / NASH / Fibrosis

Outline of Final Research Achievements

L-/-/A-/- mouse model is characterized as spontaneous LDL-C driven atherosclerosis model. We have established a NASH model by using L-/-/A-/- mouse model, in which hepatic foam cell formation of macrophages were observed with massive fibrosis.
Since the LDL fraction is hardly observed as a lipoprotein fraction in Wt mice, it will be possible to evaluate the effect of LDL on NASH pathology in our murine system. For the next steps, we are planning to evaluate the effects on cells modified by LDL, especially macrophages, in connection with coagulation/fibrinolytic factors.

Free Research Field

血液凝固線溶、脂質代謝異常、動脈硬化

Academic Significance and Societal Importance of the Research Achievements

今回作製したNASHモデルは顕著な高LDL血症を示す実験モデルであり、従来のモデルでは評価できないLDLによる病態への影響を評価することが可能となっている。今後NASHにおけるLDLコレステロールの影響に関して本モデルを用いて研究することで、現在有効な治療薬が存在しないNASHにおける有望な治療薬が開発される可能性がある。