Expression and functional analysis of let-7 for the establishment of new diagnostic and therapeutic methods for liver fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K09435
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Matsuura Kentaro 名古屋市立大学, 医薬学総合研究院(医学), 講師 (30580576)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 肝線維化 / microRNA

Outline of Final Research Achievements

Using stored samples from several chronic hepatitis C cohorts in Japan, we found that the expression level of let-7a in serum decreased with the progression of liver fibrosis and correlated well with other fibrosis markers. Cytokine and chemokine analysis was performed using stored sera from patients whose hepatitis C virus had been eliminated by treatment, and we found that serum Angiopoietin-2 and CXCL10 expression levels after completion of treatment were associated with subsequent improvement or deterioration of liver fibrosis. The expression level of let-7 in liver tissue was significantly decreased after activation of a human hepatic stellate cell line (LX-2) with several cytokines. When let-7 was transfected into LX-2, there was a trend toward suppression of gene expression related to inflammation and liver fibrosis.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

末梢血中のlet-7発現レベルが肝線維化診断マーカーとして応用できる可能性を見出した。血清サイトカイン・ケモカイン解析により、HCV排除後の肝線維化改善・非改善に関わる機構の解明につながることが期待される。細胞株を用いた検討から、let-7が肝線維化機構を抑制的に制御していること見出し、今後さらなる検討によりlet-7補充療法を肝線維化治療に応用できる可能性が考えられた。これらの期待される新規治療法は、HCV排除後や非アルコール性脂肪性肝疾患など極めて多くの患者が対象となり得、実現されればその社会的貢献は非常に大きい。