Establishment of molecular basis for improving the treatment efficacy of chronic hepatitis C and preventing the occurrence of hepatocellular carcinoma.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390187
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: HONDA Masao 金沢大学, 保健学系, 教授 (00272980)
• Co-Investigator(Kenkyū-buntansha): HORIMOTO Katsuhisa 独立行政法人産業技術総合研究所, 創薬分子プロファイリング研究センター, 副センター長 (40238803)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝炎 / 肝癌 / 自然免疫 / C型肝炎ウイルス / 肝浸潤リンパ球

Outline of Final Research Achievements

The aim of this study is to investigate how IL28B is involved in the IFN resistance in patients of chronic hepatitis C. Comparison of gene expression profiling in PBMC and liver showed that the loss of correlation of ISGs expression between PBMC and liver in IL28B minor patients. Laser capture micro dissection analysis (LCM) of hepatocyte and liver infiltrated lymphocytes combined with immune-staining of surface marker of immune cells showed that infiltration of lymphocyte into the liver was impaired in patients with IL28B minor patients. Interestingly, non-canonical wnt ligand, WNT5A was up-regulated in the liver of IL28B minor patients and WNT5A induced ISGs and stress granule protein G3BP1, and increased HCV replication. WN5A repressed the expression of chemokines and play roles in the impairment of lymphocytes infiltration in liver. The analysis of newly developed IL28B knockout mouse showed that IL28B was directly involved in the lymphocytes infiltration in liver.

Free Research Field

肝臓病学、ウイルス学、消化器癌