The metabolism of cholesterol after bile duct degeneration in lamprey

• Project/Area Number: 23792026
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Akita University
• Principal Investigator: MAYAKO Morii 秋田大学, 医学部, 助教 (10375280)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ヤツメウナギ / 胆汁酸 / 肝線維化 / コレステロール代謝 / lamprey / CYP7A1 / CYP27A1 / 肝臓 / 胆汁鬱滞性肝障害

Research Abstract

Lampreys are unique vertebrates in that they lose biliary trees entirely during the metamorphosis. Despite the biliary atresia, lampreys do not develop either biliary cirrhosis or liver dysfunction. In other vertebrates, obstruction of bile ducts results in fatality because of the cytotoxicity of bile salts. It means that lampreys have evolved to use another metabolic pathway of bile juice in order to avoid the cholestasis. However, molecular mechanism of this pathway is still unknown. The aim of this study is to investigate the way how the lamprey avoids the pathological consequence of cholestasis. We have cloned the cDNA sequences of two kinds of P450, which show high degree of homology with mammalian CYP7A1 and CYP27A1, respectively. We are now evaluating the expression levels of the mRNA for these genes in liver, gonad, gill, heart and intestine along with the temporal expression profiles from larva to adult. The present study suggests how and where bile acids are detoxified in adult lampreys. Understanding how lampreys avoid cholestasis could be valuable for progress in the treatment of human obstructive cholangiopathy.

Research Products

• [Journal Article] Characterization of a cellular retinol-binding protein from lamprey (2012)
  • Author(s): Mezaki Y, Morii M, Yoshikawa K, Yamaguchi N, Miura M, Imai K, Yoshino H, Senoo H.
  • Journal Title: Lethenteron japonicum. Comp. Biochem. Physiol. B Biochem. Mol. Biol. Volume: 161(3) Pages: 233-239
• [Journal Article] Characterization of a cellular retinol-binding protein from lamprey, Lethenteron japonicum (2012)
  • Author(s): Mezaki Y., Morii M., Yoshikawa K., Yamaguchi N., Miura M., Imai K., Yoshino H., Senoo H
  • Journal Title: Comp. Biochem. Physiol. B Biochem. Mol. Biol Volume: 161(3) Issue: 3 Pages: 233-239
  • DOI: 10.1016/j.cbpb.2011.11.011
  • NAID: 10031086293
  • Peer Reviewed
• [Journal Article] Elevated expression of transforming growth factorβ3 in carbon tetrachloride-treated rat liver and involvement of retinoid signaling (2012)
  • Author(s): Mezaki Y., Morii M., Yoshikawa K., Yamaguchi N., Satoyoshi K., Miura M., Imai K., Hebiguchi T., Habuchi T., Senoo H
  • Journal Title: Int. J. Mol. Med Volume: 29(1) Pages: 18-24
  • DOI: 10.3892/ijmm.2011.809
  • Peer Reviewed
• [Presentation] ヤツメウナギにおける胆汁排泄機構 (2013)
  • Author(s): 森井真也子、目崎喜弘、吉川究、山口典子、三浦光隆、今井克幸、蛇口琢、渡部亮、妹尾春樹、吉野祐顕
  • Organizer: 第118回日本解剖学会
  • Place of Presentation: 香川
  • Year and Date: 2013-03-30
• [Presentation] ヤツメウナギにおける胆汁酸排泄機構 (2013)
  • Author(s): 森井真也子 目崎善弘 吉川究 山口典子 三浦光隆 今井克幸 蛇口琢 渡部亮 吉野裕顕 妹尾春樹
  • Organizer: 第118回日本解剖学会総会
  • Place of Presentation: 高松
• [Presentation] The metabolism of cholesterol after bile duct degeneration in lamprey (2012)
  • Author(s): 森 井真也子、目崎喜弘、吉川究、山口典子、三浦光隆、今井克幸、蛇口琢、渡部亮、妹尾春樹、吉野祐顕
  • Organizer: 第117回日本解剖学会
  • Place of Presentation: 山梨
  • Year and Date: 2012-03-28
• [Presentation] The metabolism of cholesterol after bile duct degeneration in lamprey (2012)
  • Author(s): Morii, M., Mezaki, Y., Yamaguchi, N., Yoshikawa, K., Imai, K., Mitsutaka Miura, M., Yoshino, H, Hebiguchi, T., Asanuma, Y., Hebiguchi, T., and Senoo, H.
  • Organizer: 第117回日本解剖学会総会 第８８回日本生理学会大会・全国学術集会 合同大会
  • Place of Presentation: 甲府、山梨
• [Presentation] Reversibility of periductal fibrosis during biliary atresia in the lamprey (2011)
  • Author(s): ayako Morii, Yoshihiro Mezaki, Noriko Yamaguchi, Kiwamu Yoshikawa, Mitsutaka Miura, Katsuyuki Imai, Taku Hebiguchi, Ryo Watanabe, Hiroaki Yoshino, and Haruki Senoo
  • Organizer: 16th ISHSR International Meeting
  • Place of Presentation: Italy
  • Year and Date: 2011-09-23
• [Presentation] Reversibility of periductal fibrosis during biliary atresia in the lamprey (2011)
  • Author(s): Morii, M., Yoshino, H., Hebiguchi, T., Mezaki, Y., Yamaguchi, N., Yoshikawa, K., Miura, M., Imai, K., Senoo, H., and Hebiguchi, T.
  • Organizer: 16th International Symposium on Cells of Hepatic Sinusoid
  • Place of Presentation: Florence, Italy
• [Presentation] ω3系脂肪製剤を使用した, 短腸症候群２例の経験 (2011)
  • Author(s): 森井真也子, 吉野裕顕, 蛇口 琢, 目崎喜弘, 山口典子, 吉川 究, 三浦光隆, 今井克幸, 妹尾春樹, 蛇口達造
  • Organizer: 第48回 日本小児外科学会学術集会
  • Place of Presentation: 東京
• [Book] How do lampreys avoid cholestasis after bile duct degeneration (2011)
  • Author(s): Morii M, Mezaki Y, Yoshikawa K, Miura M, Imai K, Hebuguchi T, Watanabe R, Asanuma Y, Yoshino H, and Senoo H.
  • Publisher: Cholestasis. ed. Tripodi V. INTECH, Rijeka, Croatia
• [Book] Cholestasis-How do lampreys avoid cholestasis after bile duct degeneration- (2011)
  • Author(s): 3)Morii, M., Mezaki, Y., Yoshikawa, K., Miura, M., Imai, K., Hebuguchi, T., Watanabe, R., Asanuma, Y., Yoshino, H., and Senoo, H.
  • Publisher: ed. Tripodi V. INTECH,