Mechanisms of liver regeneration mediated by sinusoidal microcirculation in the regulation of autotaxin and lysophospholipid

• Project/Area Number: 16K09375
• 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): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肝再生 / 肝類洞再構築 / 肝類洞内皮細胞 / オートタキシン / リゾリン脂質 / リゾホスファチジン酸

Outline of Final Research Achievements

The liver is unique in its ability to regenerate in response to injury, and liver regeneration requires the mutual interaction in parenchymal hepatocyte and non-parenchymal liver cells. Among non-parenchymal cells in the liver, liver sinusoidal endothelial cells (LSECs) play a crucial role in sinusoidal remodeling at the late stage of liver regeneration.
Autotaxin (ATX) and its product, lysophosphatidic acid (LPA), are generally involved in a variety of biological functions including cellular proliferation, migration, and apoptosis. Thus, it is interesting to postulate how ATX and LPA play a role in sinusoidal remodeling at the termination of liver regeneration. In the present study, the direct relation between liver regeneration and ATX/LPA axis has not been revealed. However, since it has been reported that LSECs have the scavenger receptor for ATX, more specific analysis targeting these cells could have the potential to figure out the role of ATX/LPA axis in liver regeneration.

Academic Significance and Societal Importance of the Research Achievements

近年の再生医学の進歩は、種々の疾患領域で再生医療の実現を可能にしつつある。肝臓は古くより再生することで知られ、再生医療に適した臓器と考えられるが、肝再生医療の実現には依然大きな課題が残されている。その理由の一つには、肝臓が単一の細胞から成り立っているのではなく、実質細胞と種々の非実質細胞から構成されている為に、個々の細胞の増殖だけではなく、それらの協調により初めて肝再生が完成するという点が挙げられる。
肝類洞内皮細胞には autotaxin (ATX) のスカベンジャー・リセプタが高発現しているという報告もあり、肝再生における新しいコーディネータの役割を果たしている可能性が期待される。

Research Products

• [Journal Article] Kras promotes myeloid differentiation through Wnt/β-catenin signaling (2019)
  • Author(s): Noriko Yokoyama
  • Journal Title: FASEB Bioadvance Volume: 1 (7) Issue: 7 Pages: 435-449
  • DOI: 10.1096/fba.2019-00004
  • Description: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] KIF11 as a Potential Marker of Spermatogenesis Within Mouse Seminiferous Tubule Cross-sections (2019)
  • Author(s): Miki Hara-Yokoyama, Hidetake Kurihara, Shozo Ichinose, Hironori Matsuda, Shizuko Ichinose, Masaru Kurosawa, Norihiro Tada, Chihiro Iwahara, Kazue Terasawa, Katarzyna A Podyma-Inoue, Koichi Furukawa , Kazuhisa Iwabuchi
  • Journal Title: Journal of Histochemistry & Cytochemistry Volume: 67 Issue: 11 Pages: 813-824
  • DOI: 10.1369/0022155419871027
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of Propofol on the Production of Inflammatory Cytokines by Human Polarized Macrophages (2019)
  • Author(s): Kochiyama T, Li X, Nakayama H, Kage M, Yamane Y, Takamori K, Iwabuchi K, Inada E
  • Journal Title: Mediators of Inflammation Volume: Volume 2019 Pages: 1-13
  • DOI: 10.1155/2019/1919538
  • Peer Reviewed / Open Access
• [Journal Article] Plasma Dynorphin A Concentration Reflects the Degree of Pruritus in Chronic Liver Disease: A Preliminary Report. (2019)
  • Author(s): Moniaga CS, Iwamoto S, Kitamura T, Fujishiro M, Takahashi N, Katsunari K, Ogawa H, Tominaga M, Takamori K.
  • Journal Title: Acta Derm Venereol. Volume: 99 Issue: 4 Pages: 442-443
  • DOI: 10.2340/00015555-3139
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Glycosphingolipids and Glycosphingolipid-Enriched Lipid Rafts in Immunological Functions. (2018)
  • Author(s): Nakayama H, Nagafuku M, Suzuki A, Iwabuchi K, Inokuchi JI.
  • Journal Title: Methods Mol Biol. Volume: 1804 Issue: 23 Pages: 83-95
  • DOI: 10.1002/1873-3468.13275
  • Peer Reviewed
• [Journal Article] Gangliosides in the immune system -Role of glycosphingolipids and glycosphingolipid-enriched lipid rafts in immunological functions (2018)
  • Author(s): 1.Iwabuchi K
  • Journal Title: Gangliosides: Methods and Protocols Volume: 印刷中
  • Peer Reviewed
• [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: 80 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
• [Presentation] Role of LacCer-enriched lipid raft in LPS-induced immune responses in human neutrophils. (2018)
  • Author(s): Iwabuchi K, Nakayama H.
  • Organizer: 2nd Japan-Korea Lipid Joint Symposium, Sapporo, Japan, Sep. 2018
  • Int'l Joint Research
• [Presentation] Role of Lactosylceramide-enriched lipid microdomains in innate immune response of human phagocytes (2017)
  • Author(s): Iwabuchi K, Nakayama H
  • Organizer: 23rd International Symposium on Glycoconjugates
  • Int'l Joint Research / Invited
• [Presentation] Properties and functions of glycosphingolipid-binding molecules are highly dependent on the organization of glycosphingolipid-enriched domains (2017)
  • Author(s): Yokoyama N, Toshihide K, Inokuchi J, Alessandro P, Sandro S, Iwabuchi K
  • Organizer: Glycobiology at Nervous system
  • Int'l Joint Research / Invited
• [Presentation] A paradigm shift in innate immunity has been the recent evidence of carbohydrate-carbohydrate interactions (2017)
  • Author(s): 岩渕和久
  • Organizer: 箱守仙一郎糖鎖科学シンポジウム
  • Int'l Joint Research / Invited
• [Presentation] 病原性抗酸菌によるヒト好中球感染防御の制御機構 (2017)
  • Author(s): 岩渕和久
  • Organizer: 第2回抗酸菌研究会,東京,
  • Invited
• [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, Yokoyama N and 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
• [Book] Bile Acid in Gastroenterology: Basic and Clinical. (2017)
  • Author(s): Kitamura T, Watanabe S
  • Publisher: Springer Japan
• [Book] 慢性肝疾患における難治性そう痒症の治療の実際 (2017)
  • Author(s): 北村庸雄、髙森建二
  • Publisher: 医薬情報研究所
• [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 (2017)
  • Author(s): Nakayama H. lwabuchi K
  • Total Pages: 12
  • Publisher: Elsevier