Mechanism of liver regeneration in regulation of sinusoidal remodeling through vascular nich

• Project/Area Number: 25461011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: Kitamura Tsuneo 順天堂大学, 医学部, 先任准教授 (20231285)
• Co-Investigator(Kenkyū-buntansha): 岩渕 和久 順天堂大学, 医療看護学部, 教授 (10184897)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝再生 / 肝類洞リモデリング / 肝類洞再構築 / 肝類洞内皮細胞 / スフィンゴシン-1-リン酸 / スフィンゴシン-１-リン酸 / 肝類洞微小環境

Outline of Final Research Achievements

Liver has been well known to regenerate in response to injury as shown in two-thirds hepatectomy in rodents. It should be noted that regeneration following liver resection reflects compensative hyperplasia of cells, which is virtually proliferation and differentiation of hepatocytes. In this process, sinusoidal remodelling is important, because hepatocyte function cannot be maintained without blood flow that is formed by sinusoidal endothelial cells. In the present study, proliferation and migration of sinusoidal endothelial cells have been suggested to be crucial in liver regeneration.

Research Products

• [Journal Article] スフィンゴ糖脂質の脂質ラフトの構造と機能：ラクトシルセラミドの脂質ラフトを介した自然免疫応答 (2017)
  • Author(s): 中山仁志、岩渕和久
  • Journal Title: 生化学 Volume: 89 Pages: 62-72
  • NAID: 40021119755
  • Peer Reviewed / Open Access
• [Journal Article] Gadoxetic Acid-Enhanced MR Imaging Predicts Simeprevir-Induced Hyperbilirubinemia During Hepatitis C Virus Treatment: A Pilot Study (2016)
  • Author(s): Okubo H, Kitamura T, Ando H, Fukada H, Igusa Y, Kokubu S, Miyazaki A, Fujimura A, Shiina S, Watanabe S
  • Journal Title: J Clin Pharmacol Volume: 57 Issue: 3 Pages: 369-375
  • DOI: 10.1002/jcph.811
  • Peer Reviewed / Open Access
• [Journal Article] 胆汁酸研究の進歩と展望. 痒みの発生機序. (2016)
  • Author(s): 北村庸雄、髙森建二
  • Journal Title: 肝・胆・膵 Volume: 72 Pages: 877-891
• [Journal Article] Lipoarabinomannan binding to lactosylceramide in lipid rafts is essential for the phagocytosis of mycobacteria by human neutrophils (2016)
  • Author(s): Nakayama H, Kurihara H, Morita YS, Kinoshita T, Mauri L, Prinetti A, Sonnino S, Yokoyama N, Ogawa H, Takamori K, Iwabuchi K
  • Journal Title: Sci Signal Volume: 11 Issue: 449 Pages: 0-0
  • DOI: 10.1126/scisignal.aaf1585
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fluorescence imaging of ATP in neutrophils from patients with sepsis using organelle-localizable uorescent chemosensors. (2016)
  • Author(s): Koichiro Sueyoshi, Yuka Sumi, Yoshiaki Inoue, Yoko Kuroda, Kumiko Ishii, Hitoshi Nakayama, Kazuhisa Iwabuchi, Yasutaka Kurishita, Hajime Shigemitsu, Itaru Hamachi and Hiroshi Tanaka
  • Journal Title: Annals of Intensive Care Volume: 64 Issue: 1 Pages: 1-8
  • DOI: 10.1186/s13613-016-0175-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrative genomic and proteomic analyses identifies glycerol-3-phosphate acyltransferase as a target of low-dose ionizing radiation in EBV infected-B cells (2016)
  • Author(s): Tabe, Y., Hatanaka, Y., Nakashiro, M., Sekihara, K., Yamamoto, S., Matsushita, H., Kazuno, S., Fujimura, T., Ikegami, T., Nakanaga, K., Matsumoto, H., Ueno, T., Aoki, J., Yokomizo, T., Konopleva, M., Andreeff, M., Miida, T., Iwabuchi, K.,Sasai, K.
  • Journal Title: Int J Radiat Biol Volume: 92 Issue: 1 Pages: 24-34
  • DOI: 10.3109/09553002.2015.1106021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] No contribution of the ABCB11 p.444A polymorphism in Japanese patients with drug-induced cholestasis. (2015)
  • Author(s): Kagawa T, Hirose S, Arase Y, Oka A, Anzai K, Tsuruya K, Shiraishi K, Orii R, Ieda S, Nakazawa T, Tomita K, Hokari R, Miura S, Ebinuma H, Saito H, Kitamura T, Horie Y, Okuse C, Wasada M, Inoko H, Tohkin M, Saito Y, Maekawa K, Takikawa H, Mine T
  • Journal Title: Drug Metabolism and Disposition Volume: 43 Issue: 5 Pages: 691-697
  • DOI: 10.1124/dmd.114.061325
  • Peer Reviewed
• [Journal Article] Direct interaction, instrumental for signaling processes, between LacCer and Lyn in the lipid rafts of neutrophil-like cells. (2015)
  • Author(s): Chiricozzi E, Ciampa MG, Brasile G, Compostella F, Prinetti A, Nakayama H, Ekyalongo RC, Iwabuchi K, Sonnino S, Mauri L
  • Journal Title: Journal of Lipid Research Volume: 56 Issue: 1 Pages: 129-41
  • DOI: 10.1194/jlr.m055319
  • Peer Reviewed
• [Journal Article] Transbilayer distribution of lipids at nano scale. (2015)
  • Author(s): Murate M, Abe M, Kasahara K, Iwabuchi K, Umeda M, Kobayashi T
  • Journal Title: J Cell Sci Volume: 128 Pages: 1627-1638
  • DOI: 10.1242/jcs.163105
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Properties and functions of lactosylceramide from mouse neutrophils (2015)
  • Author(s): Iwabuchi K, Masuda H, Kaga N, Nakayama H, Matsumoto R, Iwahara C, Yoshizaki F, Tamaki Y, Kobayashi T, Hayakawa T, Ishii K, Yanagida M, Ogawa H, Takamori K
  • Journal Title: Glycobiology Volume: 25 Issue: 6 Pages: 655-668
  • DOI: 10.1093/glycob/cwv008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Organization and functions of glycolipid-enriched microdomains in phagocytes (2015)
  • Author(s): Ekyalongo RC, Nakayama H, Kina K, Kaga N, Iwabuchi K
  • Journal Title: Biochim Biophys Acta Volume: 1851 Pages: 90-97
  • Peer Reviewed
• [Journal Article] Recessive Inheritance of Population-Specific Intronic LINE-1 Insertion Causes a Rotor Syndrome Phenotype (2015)
  • Author(s): Tatehiro Kagawa, Akira Oka, Yoshinao Kobayashi, Yoichi Hiasa, Tsuneo Kitamura, Hiroshi Sakugawa, Yukihiko Adachi, Kazuya Anzai, Kota Tsuruya, Yoshitaka Arase, Shunji Hirose, Koichi Shiraishi, Takashi Shiina, Tadayuki Sato, Ting Wang, Masayuki Tanaka, Hideki Hayashi et al.
  • Journal Title: Human Mutation Volume: 36 Issue: 3 Pages: 327-332
  • DOI: 10.1002/humu.22745
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pseudomonas-derived ceramidase induces production of inflammatory mediators from human keratinocytes via sphingosine-1-phosphate (2014)
  • Author(s): Oizumi A, Nakayama H, Okino N, Iwahara C, Kina K, Matsumoto R, Ogawa H, Takamori K, Ito M, Suga Y, Iwabuchi K.
  • Journal Title: PLoS One. Volume: 9(2) Issue: 2 Pages: 89402-89402
  • DOI: 10.1371/journal.pone.0089402
  • Peer Reviewed / Open Access
• [Journal Article] Pseudomonas-derived ceramidase induces production of inflammatory mediators from human keratinocytes via sphingosine-1-phosphate (2014)
  • Author(s): Oizumi A, Nakayama H, Okino N, Iwahara C, Kina K, Matsumoto R, Ogawa H, Takamori K, Ito M, Suga Y, Iwabuchi K.
  • Journal Title: PLoS One Volume: 25
  • Peer Reviewed
• [Presentation] 抗体や毒素を用いたスフィンゴ糖脂質の脂質マイクロドメインの構造と機能解析について (2016)
  • Author(s): 横山紀子, 石井久美子, 小林俊秀, 加藤幸成, 井ノ口仁一, 岩渕和久
  • Organizer: 第9回セラミド研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-10-27
• [Presentation] 結核菌による LacCer を介した食胞成熟回避機構について (2016)
  • Author(s): 中山仁志, 横山紀子, 岩渕和久
  • Organizer: 第9回セラミド研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-10-27
• [Presentation] ヒトマクロファージにおけるプロポフォールの抗炎症効果 (2016)
  • Author(s): 河内山宰, 渡部晃士, 中山仁志, 岩渕和久, 神山洋一郎
  • Organizer: 第89回日本生化学会年会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] ヒト好中球におけるLPS依存性の貪食はLacCerの脂質ラフトに会合したCD14だけが関与する (2016)
  • Author(s): 中山仁志, 横山紀子, 石井久美子, 鹿毛まどか, 栗原秀剛, 岩渕和久
  • Organizer: 第89回日本生化学会年会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] Lactosylceramide is a key player in immunological functions of human neutrophils (2016)
  • Author(s): Iwabuchi K, Nakayama H.
  • Organizer: Cell Synposia: 100 year of Phagocytes
  • Place of Presentation: Sicily, Italy
  • Year and Date: 2016-09-19
  • Int'l Joint Research
• [Presentation] Human neutrophils phagocytose mycobacteria through interactions between LacCer and α1,2-monomannose side (2016)
  • Author(s): Iwabuchi K, Nakayama H, Yokohama N, Iwabuchi K
  • Organizer: The Society For Leukocyte Biology’s 49th Annual Meeting and “Neutrophil 2016
  • Place of Presentation: Verona, Italy
  • Year and Date: 2016-09-15
  • Int'l Joint Research
• [Presentation] Organization and immunological functions of Lactosylceramide-enriched lipid rafts (2016)
  • Author(s): Nakayama H, Yokoyama N and Ishii K
  • Organizer: The Society For Leukocyte Biology’s 49th Annual Meeting and “Neutrophil 2016”
  • Place of Presentation: Verona, Italy
  • Year and Date: 2016-09-15
  • Int'l Joint Research
• [Presentation] HILIC-ESI-MS によるグルコース化脂質異性体の定性・定量分 析とその臨床応用 (2016)
  • Author(s): 中嶋和紀, 秋山央子, 伊藤恵実, 岩渕和久, 湯澤由紀夫, 平林 義雄
  • Organizer: 第35回日本糖質学会年会
  • Place of Presentation: 高知
  • Year and Date: 2016-09-01
• [Presentation] 結核菌による LacCerを利用したヒト好中球の食胞成熟回避機構について (2016)
  • Author(s): 岩渕和久, 中山仁志, 横山紀 子, 石井久美 子
  • Organizer: 第35回日本糖質学会年会
  • Place of Presentation: 高知
  • Year and Date: 2016-09-01
• [Presentation] 結核菌がヒト好中球による殺菌を回避する機構について (2016)
  • Author(s): 岩渕和久, 中山仁志, 横山紀子, 石井久美子
  • Organizer: 第9回スフィンゴテラピー研究会
  • Place of Presentation: 金沢
  • Year and Date: 2016-07-14
• [Presentation] ホスファチジルグルコシドを介した白血球分化について (2016)
  • Author(s): 鹿毛まどか, ルーディ チミンチ イキャロンゴ ボ ラウェレ, 横山紀子, 中山仁志, 平林義雄, 岩渕和久
  • Organizer: 第9回スフィンゴテラピー研究会
  • Place of Presentation: 金沢
  • Year and Date: 2016-07-14
• [Presentation] ホスファチジルグルコシドを介したアポトーシス制御について (2016)
  • Author(s): 岩渕和久, ルーディ チミンチ イキャロンゴ ボ ラウェレ, 横山紀子, 中山仁志, 鹿毛まどか, 平林義雄
  • Organizer: 第58回日本脂質生化学会年会
  • Place of Presentation: 秋田
  • Year and Date: 2016-06-09
• [Presentation] ホスファチジルグルコシドを介した好中球分化について (2015)
  • Author(s): ルーディ チミンチ イキャロンゴ ボ ラウェレ、横山紀子、中山仁志、平林義雄、岩渕和久
  • Organizer: 第57回日本脂質生化学会
  • Place of Presentation: 一橋大学一橋講堂
  • Year and Date: 2015-05-28 – 2015-05-29
• [Presentation] 抗体や毒素を用いたスフィンゴ糖脂質に富む膜マイクロドメインの構造と機能解析について (2014)
  • Author(s): 岩渕和久、玉木友樹、増田浩美、中山仁志、石井久美子、小林俊秀
  • Organizer: 第7回セラミド研究会学術集
  • Place of Presentation: 北海道大学
  • Year and Date: 2014-10-30 – 2014-10-31
• [Presentation] ヒト好中球におけるCD14依存性LPSシグナルはラクトシルセラミドのマイクロドメインにより仲介される (2014)
  • Author(s): 中山仁志、玉木友樹、ルーディ チミンチ イキャロンゴ ボ ラウェレ、岩渕和久
  • Organizer: 第7回セラミド研究会学術集
  • Place of Presentation: 北海道大学
  • Year and Date: 2014-10-30 – 2014-10-31
• [Presentation] 抗体や毒素を用いた糖脂質膜マイクロドメインの構造と機能解析について (2014)
  • Author(s): 岩渕和久、玉木友樹、増田浩美、岩原知博、松本亮、中山仁志、小林俊秀、石井 久美子、早川智広、小川秀興、髙森建二
  • Organizer: 第33回日本糖質学会年会
  • Place of Presentation: 名古屋大学豊田講堂
  • Year and Date: 2014-08-10 – 2014-08-12
• [Book] Bile Acids and NAFLD/NASH. Bile Acid in Gastroenterology (2017)
  • Author(s): Kitamura T, Watanabe S
  • Total Pages: 11
  • Publisher: Springer Japan
• [Book] Molecular mechanisms underlying the immunological activities of glycosphingolipid-enriched lipid rafts in phagocytes, Reference Modules entitled Chemistry, Molecular Sciences and Chemical Engineering (2017)
  • Author(s): Nakayama H, Iwabuchi K
  • Total Pages: 12
  • Publisher: Elsevier