The effect of sirtuin on the pathogenesis of hepatitis B virus-related liver disease

• Project/Area Number: 26860491
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Chiba University
• Principal Investigator: Nakamoto Shingo 千葉大学, 大学院医学研究院, 助教 (90586596)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: B型肝炎ウイルス / 肝線維化 / B型肝炎

Outline of Final Research Achievements

Hepatitis B virus (HBV) can cause chronic infection in the liver. It can lead to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Cellular aging may be associated with HBV-related liver diseases. Knockdown of sirtuins, genes associated with age-related diseases, was associated with the activity of hepatic stellate cell. HBV replication altered the activity of hepatic stellate cell. Cellular aging assay suggested that X protein expression may have a potential to alter cellular aging. Lack of sirtuin using CRISPR/Cas system affected HBV replication. The results suggested that sirtuin may have a role in HBV-related liver disease.

Research Products

• [Journal Article] Discrepancy between Hepatitis C Virus Genotypes and NS4-Based Serotypes: Association with Their Subgenomic Sequences. (2017)
  • Author(s): Nan Nwe Win, Shingo Nakamoto, Tatsuo Kanda, Hiroki Takahashi, Azusa Takahashi-Nakaguchi, Shin Yasui, Masato Nakamura, Shuang Wu, Fumio Imazeki, Shigeru Mikami, Osamu Yokosuka, Tohru Gonoi, Hiroshi Shirasawa
  • Journal Title: International Journal of Molecular Sciences Volume: 18(1) Issue: 1 Pages: 172-172
  • DOI: 10.3390/ijms18010172
  • Peer Reviewed / Open Access
• [Journal Article] Cooperative effects of hepatitis B virus and TNF may play important roles in the activation of metabolic pathways through the activation of NF-κB (2016)
  • Author(s): Wu S, Kanda T, Nakamoto S, Jiang X, Nakamura M, Sasaki R, Haga Y, Shirasawa H, Yokosuka O.
  • Journal Title: Int J Mol Med. Volume: 38 Issue: 2 Pages: 475-481
  • DOI: 10.3892/ijmm.2016.2643
  • Peer Reviewed / Open Access
• [Journal Article] Possible Involvement of Hepatitis B Virus Infection of Hepatocytes in the Attenuation of Apoptosis in Hepatic Stellate Cells. (2016)
  • Author(s): Sasaki R, Kanda T, Nakamura M, Nakamoto S, Haga Y, Wu S, Shirasawa H, Yokosuka O.
  • Journal Title: PLoS One. Volume: 11 Issue: 1 Pages: 1-17
  • DOI: 10.1371/journal.pone.0146314
  • Peer Reviewed / Open Access
• [Journal Article] The sirtuin inhibitor sirtinol inhibits hepatitis A virus (HAV) replication by inhibiting HAV internal ribosomal entry site activity. (2015)
  • Author(s): Kanda T, Sasaki R, Nakamoto S, Haga Y, Nakamura M, Shirasawa H, Okamoto H, Yokosuka O.
  • Journal Title: Biochem Biophys Res Commun. Volume: 466 Issue: 3 Pages: 567-571
  • DOI: 10.1016/j.bbrc.2015.09.083
  • Peer Reviewed / Open Access
• [Journal Article] Reactivation of hepatitis B virus in hematopoietic stem cell transplant recipients in Japan: efficacy of nucleos(t)ide analogues for prevention and treatment. (2014)
  • Author(s): Nakamoto S, Kanda T, Nakaseko C, Sakaida E, Ohwada C, Takeuchi M, Takeda Y, Mimura N, Iseki T, Wu S, Arai M, Imazeki F, Saito K, Shirasawa H, Yokosuka O.
  • Journal Title: Int J Mol Sci Volume: 15 Issue: 11 Pages: 21455-67
  • DOI: 10.3390/ijms151121455
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity. (2014)
  • Author(s): Jiang X, Kanda T, Wu S, Nakamura M, Miyamura T, Nakamoto S, Banerjee A, Yokosuka O.
  • Journal Title: World J Gastroenterol. Volume: 20 Issue: 23 Pages: 7197-7206
  • DOI: 10.3748/wjg.v20.i23.7197
  • Peer Reviewed / Open Access
• [Journal Article] Hepatitis C virus NS5A inhibitors and drug resistance mutations. (2014)
  • Author(s): Nakamoto S, Kanda T, Wu S, Shirasawa H, Yokosuka O.
  • Journal Title: World J Gastroenterol. Volume: 20 Issue: 11 Pages: 2902-2912
  • DOI: 10.3748/wjg.v20.i11.2902
  • Peer Reviewed / Open Access
• [Presentation] Association between Sirtuins Expression and Hepatocellular Carcinoma (2016)
  • Author(s): Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Reina Sasaki, Yuki Haga, Masato Nakamura, Nan Nwe Win, Osamu Yokosuka, Hiroshi Shirasawa
  • Organizer: 25th Asian Pacific Association for the Study of the Liver (APASL 2016)
  • Place of Presentation: International Convention Center Pamir (Tokyo, Minato-ku)
  • Year and Date: 2016-02-22
  • Int'l Joint Research
• [Presentation] B型肝炎ウイルスにおけるエピジェネティック転写制御機構の検討 (2016)
  • Author(s): 中本晋吾、神田達郎、佐々木玲奈、呉霜、Nan Nwe Win、芳賀祐規、中村昌人、横須賀收、白澤浩
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: 東京ベイ幕張ホール（千葉県千葉市）
• [Presentation] エピジェネティック修飾によるB型肝炎ウイルス増殖制御に関する検討 (2016)
  • Author(s): 中本晋吾、神田達郎、横須賀收
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
• [Presentation] Inhibition of epigenetic regulators affects hepatitis B virus (HBV) replication and Hepatitis B surface (HBs) antigen production. (2015)
  • Author(s): Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Yuki Haga, Reina Sasaki, Masato Nakamura, Hiroshi Shirasawa, Osamu Yokosuka
  • Organizer: The 66th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2015
  • Place of Presentation: Moscone West Convention Center, San Francisco, USA
  • Year and Date: 2015-11-16
  • Int'l Joint Research
• [Presentation] Screening of epigenetic compound library using primary hepatocyte persistantly infecting hepatitis B virus (2015)
  • Author(s): Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Xia Jiang,Yuki Haga, Reina Sasaki, Masato Nakamura, Hiroshi, Shirasawa, Osamu Yokosuka
  • Organizer: 24th Conference of the Asian Pacific Associaton for the Study of the Liver
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2015-03-13
• [Presentation] 高齢者ジェノタイプ1型C型慢性肝炎に対するシメプレビルを含む3剤併用療法に関する検討 (2014)
  • Author(s): 中本晋吾, 神田達郎, 新井誠人, 太和田暁之, 千葉哲博, 今関文夫, 三上繁, 横須賀收
  • Organizer: JDDW2014
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2014-10-24