| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
The response of chronic hepatitis C (CHC) to IFN treatment is hampered in patients with advanced liver fibrosis. TGF-β plays an important role in fibrosis development, but its role in IFN signaling is unclear. I investigated the role of TGF-β on IFN signaling in HCV replication. TGF-β impaired IFN signaling by activating Socs3-mediated IFN inhibitory signaling via Foxo3a promoter activation by c-Jun binding. BCAAs could be a new therapeutic candidate to augment IFN signaling in HCV replication in patients with advanced CHC.
I also investigated the functional relevance of IL28B on the innate antiviral system and HCV replication. Gene expression profiling of primary hepatocytes treated with IFNα, IL28B, or both in combination revealed that LECT2, which enhances the innate immune response and suppresses HCV replication, was specifically induced by IL28B. LECT2 might participate in prolonged ISG induction by IL28B and in the unique innate antiviral immune system of IL28B.
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