Pathological deterioration of liver component cells by hepatitis B virus infection and the mechanism of hepatocarcinogenesis
| Project/Area Number |
17K09414
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | B型肝炎ウイルス / 肝細胞癌 / 核酸アナログ / Notchシグナル / HBV cccDNA / 肝線維化 / 肝細胞がん / 細胞分離 / ウィルス |
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| Outline of Final Research Achievements |
Liver tissue consists from endothelial cells, bile duct cells, immune cells and hepatocyte. Hepatitis B virus induces hepatitis and liver cancer, but the interaction and virus infection related signaling between these component cells are not still clarified. We analyzed these interactions by measuring gene expression in each component cells using single cell gene analysis. We clarified the intercellular signaling including Notch signaling activation and this interaction resulted in the involvement of transcription factors in hepatitis B virus infected cells. Results of analyzing clinical liver tissue found that these transcription factors or intercellular signaling were affected under nucleos(t)ide analogues treatment. In conclusion, intercellular signaling were found to be important in hepatitis B virus infected liver tissue.
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| Academic Significance and Societal Importance of the Research Achievements |
核酸アナログ製剤によりB型肝炎の鎮静化がなされるが、治療後も肝細胞核内に完全二本鎖の形でウイルスが残存しており、発癌や再活性化を引き起こす。この問題を解決するために、肝組織内の構成細胞における感染による変化、細胞間の相互作用やシグナル伝達系を明確にした。本研究はこのウイルス残存の問題を解決し、従来の薬剤では解決できない創薬にも関連するので、社会的意義のある研究となった。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Serum aldo-keto reductase family 1 member B10 predicts advanced liver fibrosis and fatal complications of nonalcoholic steatohepatitis.2019
Author(s)
M Kanno, K Kawaguchi, M Honda, R Horii, H Takatori, T Shimakami, K Kitamura, K Arai, T Yamashita, Y Sakai, T Yamashita, E Mizukoshi, S Kaneko.
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Journal Title
J Gastroenterol
Volume: -
Issue: 6
Pages: 549-557
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Analysis of the liver functional reserve of patients with advanced hepatocellular carcinoma undergoing sorafenib treatment: Prospects for regorafenib therapy.2018
Author(s)
Terashima T, Yamashita T, Sunagozaka H, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
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Journal Title
Hepatol Res
Volume: 48
Issue: 12
Pages: 956-966
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts hepatocellular carcinoma incidence and recurrence in nucleos(t)ide analogue therapy for chronic hepatitis B.2017
Author(s)
Kawaguchi K, Honda M, Ohta H, Terashima T, Shimakami T, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Komura T, Unoura M, Kaneko S
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Journal Title
J Gastroenterol
Volume: ePub ahead
Issue: 6
Pages: 740-751
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell.2017
Author(s)
Sakai Y, Takamura M, Seki A, Sunagozaka H, Terashima T, Komura T, Yamato M, Miyazawa M, Kawaguchi K, Nasti A, Mochida H, Usui S, Otani N, Ochiya T, Wada T, Honda M, Kaneko S
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Journal Title
Regenerative Therapy
Volume: 6
Pages: 52-64
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Serum aldo-keto reductase family 1 member B10 predicts HBV-related hepatocellular carcinoma during nucleos(t)ide analogue treatment2019
Author(s)
Kazunori Kawaguchi, Masao Honda, Noriaki Orita, Masataka Kanno, Rika Horii, Kouki Nio, Takeshi Terashima, Tetsuro Shimakami, Kuniaki Arai, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Shuichi Kaneko
Organizer
The Liver Meeting 2019
Related Report
Int'l Joint Research
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[Presentation] mTORC2-Akt phosphorylation is associated with Notch signaling activation by nucleotide analogues but not nucleoside analogues for chronic HBV infection2018
Author(s)
Kazunori Kawaguchi, Zijing Wang, Masao Honda, Takayoshi Shirasaki, Hikari Okada, Ying-Yi Li, Kazuhisa Murai, Kouki Nio, Tetsuro Shimakami, Taro Yamashita, Kazuyuki Kuroki, Shinichi Hashimoto, Seishi Murakami, Shuichi Kaneko
Organizer
2018 HBV meeting
Related Report
Int'l Joint Research
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[Presentation] mTORC2-related protein kinase B phosphorylation is associated with Notch signaling activation by nucleotide analogues for chronic hepatitis B virus infection2018
Author(s)
Kazunori Kawaguchi, Zijing Wang, Masao Honda, Hikari Okada, Takayoshi Shirasaki, Kouki Nio, Tetsuro Shimakami, Kuniaki Arai, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Shuichi Kaneko
Organizer
2018 AASLD
Related Report
Int'l Joint Research
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[Presentation] Nucleos(t)ide analogues and interferon affect intranuclear HBV genome in vitro via Notch signaling modification, independent of the ubiquitin-proteasome system2017
Author(s)
Kawaguchi Kazunori, Wang Zijing, Honda Masao, Shirasaki Takayoshi, Okada Hikari, Shimakami Tetsuro, Nio Kouki, Arai Kuniaki, Yamashita Taro, Sakai Yoshio, Yamashita Tatsuya, Mizukoshi Eishiro, Kaneko Shuichi
Organizer
The Liver Meeting 2017
Related Report
Int'l Joint Research
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