Liver regeneration is dependent on sugar chain

• Project/Area Number: 23651196
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: Tohoku Pharmaceutical University
• Principal Investigator: GU Jianguo 東北薬科大学, 薬学部, 教授 (40260369)
• Co-Investigator(Kenkyū-buntansha): FUKUDA Tomohiko 東北薬科大学, 薬学部, 准教授 (40433510)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: α1,6フコース / Fut8 / liver regeneration / 糖鎖 / 肝再生 / 増殖因子受容体 / 肝がん / 糖転移酵素 / Fut8欠損マウス / 細胞増殖

Research Abstract

The expression of alpha1,6-fucosyltransferase (Fut8) and its products (alpha1,6-fucosylated N-glycans) are known to be elevated in both liver and serum during the process of hepatocarcinogenesis (HCC). However, the regulatory mechanism of high Fut8 expression in HCC progression remains poorly understood. In fact, cell proliferation plays a crucial role in the process of liver regeneration. Therefore, to examine effects of Fut8 on cell growth in vivo, we performed a partial hepatectomy on wild type and Fut8 knockout mice to induce liver regeneration. Interestingly, the speed of liver regeneration in Fut8 knockout mice was significantly slower than that in wild-type mice. Interestingly, an oral administration of L-fucose significantly accelerated liver regeneration of the Fut8-hetero mice, but did not affect the sham mice. These results further suggest that Fut8 and its products are important for cell proliferation in liver regeneration.

Research Products

• [Journal Article] α1, 6-Fucosylation regulates neurite formation via the activin/phospho-Smad2 pathway in PC12 cells : the implicated dual effects of Fut8 for TGF-β/activin-mediated signaling (2013)
  • Author(s): Gu, W., Fukuda, T., Isaji, T., Hashimoto, H., Wang., Y and Gu, J
  • Journal Title: FASEB J Volume: 27 Pages: 3947-3958
• [Journal Article] α1,6-Fucosylation regulates neurite formation via the activin/phospho-Smad2 pathway in PC12 cells: the implicated dual effects of Fut8 for TGF-β/activin-mediated signaling. (2013)
  • Author(s): Gu, W., Fukuda, T., Isaji, T., Hashimoto, H., Wang., Y and Gu, J.
  • Journal Title: FASEB J Volume: 27 Issue: 10 Pages: 3947-3958
  • DOI: 10.1096/fj.12-225805
  • Peer Reviewed
• [Journal Article] Anti-tumor effects of exogenous ganglioside GM3 on bladder cancer in an orthotopic cancer model. (2013)
  • Author(s): Wang, H., et al
  • Journal Title: Urology Volume: 81 Issue: 1 Pages: 210-210
  • DOI: 10.1016/j.urology.2012.08.015
  • Peer Reviewed
• [Journal Article] Core fucosylation of mu heavy chains regulates the assembly of precursor B cell receptors and its intracellular signaling (2012)
  • Author(s): Li, W., Liu, Q., Pang, Y., Jin, J., Wang, H., Cao, H., Li, Z., Wang, X., Ma, B., Chi, Y., Wang, R., Kondo, A., Gu, J. and Taniguchi, N
  • Journal Title: J Biol Chem Volume: 287 Pages: 2500-2508
• [Journal Article] Potential roles of N-glycosylation in cell adhesion. (2012)
  • Author(s): Gu, J., et al
  • Journal Title: Glycoconj J Volume: 29 Issue: 8-9 Pages: 599-607
  • DOI: 10.1007/s10719-012-9386-1
  • Peer Reviewed
• [Journal Article] Core fucosylation of mu heavy chains regulates the assembly of precursor B cell receptors and its intracellular signaling. (2012)
  • Author(s): Li, W., et al.
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 2500-2508
  • Peer Reviewed
• [Journal Article] Roles of N-acetylglucosaminyltransferase III in epithelial-to-mesenchymal transition induced by TGF-β1 in epithelial cell lines. (2012)
  • Author(s): Xu, Q., et al.
  • Journal Title: J. Biol. Chem. Volume: 287
  • Peer Reviewed
• [Journal Article] Potential roles of N-glycosylation in cell adhesion (2012)
  • Author(s): Gu, J., et al.
  • Journal Title: Glycoconj. J. Volume: 29
  • Peer Reviewed
• [Journal Article] α1,6-Fucosyltransferase-deficient mice exhibit multiple behavioral abnormalities associated with a schizophrenia-like phenotype: importance of the balance between the dopamine and serotonin systems. (2011)
  • Author(s): Fukuda, T., et al
  • Journal Title: J. Biol. Chem. Volume: 286 Pages: 18434-43
  • Peer Reviewed
• [Journal Article] N-glycosylation of beta4 integrin controls the adhesion and motility of keratinocytes. (2011)
  • Author(s): Kariya, Y. and Gu, J.
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Presentation] Roles of α1,6-fucosyltransferase (Fut8) in liver tissues (2014)
  • Author(s): 顧 建国
  • Organizer: Nantong University Medical School Seminar
  • Place of Presentation: 中国南通大学
  • Invited
• [Presentation] α1, 6-fucosylation and its relationship with diseases (2013)
  • Author(s): 顧建国
  • Organizer: 北京大学化学研究所セミナー
  • Place of Presentation: 北京
• [Presentation] 肝臓がん形成および肝再生におけるα1, 6 フコシル化の重要性 (2013)
  • Author(s): 王玉琴, 福田友彦, 顧威, 伊左治知弥, 三善英知, 顧建国
  • Organizer: 第7回東北糖鎖研究会
  • Place of Presentation: 新潟
• [Presentation] α1,6-fucosylation and its relationship with diseases (2013)
  • Author(s): 顧 建国
  • Organizer: 北京大学化学研究所セミナー
  • Place of Presentation: 北京大学
  • Invited
• [Presentation] 肝臓がん形成および肝再生におけるα1,6フコシル化の重要性 (2013)
  • Author(s): 王玉琴、福田友彦、顧威、伊左治知弥、三善英知、顧建国
  • Organizer: 第７回東北糖鎖研究会
  • Place of Presentation: 新潟
• [Presentation] Functional analysis of N-glycosylation and its related diseases (2012)
  • Author(s): 顧建国
  • Organizer: 上海市薬理学会第十三回学術年会
  • Place of Presentation: 上海
  • Invited
• [Presentation] N-glycosylation of integrins and cancer metastasis (2012)
  • Author(s): 顧建国
  • Organizer: 浙江省がんセンターセミナー
  • Place of Presentation: 杭州
  • Invited
• [Presentation] N-結合型糖鎖の機能発現・調節機構とその意義に関して (2012)
  • Author(s): 顧建国
  • Organizer: 平成24年東北薬科大学分子生体膜研究所シンポジウム
  • Place of Presentation: 仙台
• [Presentation] N-acetylglucosaminyltransferase III (GnT-III) expression and its role in epithelial-to-mesenchymal transition (EMT) (2011)
  • Author(s): 顧建国
  • Organizer: The 3rd Asian Communications of Glycobiology and Glycotechnology (ACGG)(招待講演)
  • Place of Presentation: 上海
• [Presentation] N-結合型糖鎖の機能制御および疾患への関わり (2011)
  • Author(s): 顧建国
  • Organizer: 糖鎖科学研究所講演会(招待講演)
  • Place of Presentation: 東海大学
• [Presentation] 癌遺伝子GOLPH3によるインテグリンbeta1の糖鎖変化とその機能調節 (2011)
  • Author(s): 近藤円、伊左治知弥、福田友彦、顧建国
  • Organizer: 第５回東北糖鎖研究会
  • Place of Presentation: 東北大学
• [Presentation] 細胞間接着における糖転移酵素GnT-IIIの発現と機能 (2011)
  • Author(s): 顧建国
  • Organizer: 第５回東北糖鎖研究会
  • Place of Presentation: 東北大学
• [Presentation] GOLPH3 によるインテグリンβ1の糖鎖付加および機能制御 (2011)
  • Author(s): 伊左治知弥、顧建国
  • Organizer: 第７０回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] インテグリンα3鎖に付加されたN-結合型糖鎖の多機能性 (2011)
  • Author(s): 陸瑩瑩、伊左治知弥、福田友彦、顧建国
  • Organizer: 第８４回日本生化学会
  • Place of Presentation: 京都国際会議場
• [Presentation] GOLPH3 によるインテグリンβ1の糖鎖付加および機能制御 (2011)
  • Author(s): 伊左治知弥、近藤円、福田友彦、顧建国
  • Organizer: 第８４回日本生化学会
  • Place of Presentation: 京都国際会議場
• [Presentation] β４インテグリンの機能発現におけるN-結合型糖鎖の役割 (2011)
  • Author(s): 苅谷慶喜、顧建国
  • Organizer: 第８４回日本生化学会
  • Place of Presentation: 京都国際会議場
• [Presentation] インテグリンに付加された糖鎖の意義について (2011)
  • Author(s): 伊左治知弥、陸瑩瑩、福田友彦、顧建国
  • Organizer: 第77回日本生化学会 東北支部会
  • Place of Presentation: 東北大学
• [Presentation] Fut8欠損マウスにみられる統合失調症様行動と脳内神経伝達物質バランスの変化 (2011)
  • Author(s): 福田友彦、伊左治知弥、顧建国
  • Organizer: 第３０回日本糖質学会年会
  • Place of Presentation: 長岡
• [Presentation] N-アセチルグルコサミン転移酵素IIIの発現調節とEMTにおける役割 (2011)
  • Author(s): 顧建国
  • Organizer: 第３０回日本糖質学会年会
  • Place of Presentation: 長岡
• [Presentation] β４インテグリンの機能発現におけるN-結合型糖鎖の役割 (2011)
  • Author(s): 苅谷慶喜、顧建国
  • Organizer: 第43回日本結合組織学会学術大会・第58回マトリックス研究会大会合同学術集会
  • Place of Presentation: 大分県別府市
• [Book] α1, 6-Fucosyltransferase欠損マウスに見られた統合失調症様行動とその解析, 実験医学 (2013)
  • Author(s): 顧建国, 谷口直之, 福田友彦
  • Publisher: 羊土社
• [Book] α1,6-Fucosyltransferase欠損マウスに見られた統合失調症様行動とその解析 (2013)
  • Author(s): 顧建国、谷口直之、福田友彦
  • Total Pages: 6
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/drg/index.html