The effect of RNA binding proteins on regulatory mechanisms of anti-fibrotic and anti-inflammatory miRNA biogenesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16523
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kochi University
• Principal Investigator: Higuchi Takuma 高知大学, 教育研究部医療学系基礎医学部門, 助教 (10754567)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: miRNA / RNA結合タンパク質 / NF90 / NASH / 線維化 / 炎症

Outline of Final Research Achievements

NF90-NF45, a complex of RNA binding proteins (RBPs), suppresses multiple miRNA biogenesis. We found that expression levels of NF90-NF45 were elevated in the liver of Non-alcoholic state hepatitis (NASH) model mice. However, the influence of NF90-NF45 on fibrosis and inflammation of the liver under NASH is still unclear. In this study, we found the possibility that NF90-NF45 induced suppression of anti-fibrotic miRNA (miR-483-5p) production, leading to up-regulation of Timp2, which is a metalloproteinase inhibitor and direct target of miR-483-5p, resulting in liver fibrosis. Moreover, we generated liver-specific NF90 deficient mice. To confirm the RBPs-miRNA-fibrosis axis, we are attempting to analyze the fibrosis and inflammation of the liver in this mouse by immunohistochemistry, biochemical blood test, and glucose tolerance test.

Free Research Field

分子生物学、生化学

Academic Significance and Societal Importance of the Research Achievements

非アルコール性の脂肪肝疾患の一つであるNASHは、肝硬変や肝細胞がんへと進行することから予後不良であるが、現時点でNASHに対する治療法は十分に確立されていない。加えて、NASHの発症・増悪化を司る肝炎・肝線維化進展の制御メカニズムについても不明な点が多く残されている。本研究結果から、NASHモデルマウス肝臓におけるNF90-NF45の発現増加がmiRNAの産生抑制を介して肝臓の線維化を制御する可能性が見出された。本研究成果はNASHに対する新規治療法開発の礎となることが期待される。