糖鎖高分子を用いた細胞機能の制御、解明とその応用研究
キーワード：ガン細胞、糖鎖、高分子、細胞機能制御
2013.12～2023.11.
| 伊勢 裕彦（いせ ひろひこ） | データ更新日：2023.12.06 |
主な研究テーマ
研究業績
主要原著論文
| 1. | H. Ise, Y. Araki, I. Song, G. Akatsuka, N-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells, Glycobiology, https://doi.org/10.1093/glycob/cwac067, 33, 1, 17-37, 2023.01. |
| 2. | Beomju Hwang, Hirohiko Ise, Multimeric conformation of type III intermediate filaments but not the filamentous conformation exhibits high affinity to lipid bilayers, Genes Cells, https://doi.org/10.1111/gtc.12768, 25, 6, 413-426, 2020.04. |
| 3. | Hirohiko Ise ,Kumiko Matsunaga, Marie Shinohara, and Yasuyuki Sakai, Improved Isolation of Mesenchymal Stem Cells Based on Interactions between N-Acetylglucosamine-Bearing Polymers and Cell-Surface Vimentin, Stem Cells International, https://doi.org/10.1155/2019/4341286, 2019, 2019, 1-13, 2019.11. |
| 4. | Hirohiko Ise, Vimentin’s N-Acetylglucosamine-Binding Activity: Its Physiological Function, Trends Glycosci. Glycotechnol., 29, 169, E71-E79, 2017.09, Vimentin is known as a cytoskeletal protein that is expressed in mesenchymal and skeletal muscle tissues and plays an important role in the maintenance of the cytoplasmic architecture and cellular integrity. Moreover, vimentin is implicated in various cellular signal transduction pathways involved in cell proliferation and cell migration. Vimentin is highly expressed in lesion sites of various chronic diseases such as fibrosis, cancer, and autoimmune diseases. Vimentin’s high expression in various chronic diseases led to investigate its involvement in pathological mechanisms in chronic diseases. We recently reported that vimentin possesses N-acetyl-D-glucosamine (GlcNAc)-binding activity on cell surfaces. In this review, we describe vimentin’s GlcNAc-binding activity and discuss our hypothesis regarding its physiological relevance.. |
| 5. | Hirohiko Ise, Sadanori Yamasaki, Kazuaki Sueyoshi, Yoshiko Miura, Elucidation of GlcNAc-binding properties of type III intermediate filament proteins, using GlcNAc-bearing polymers, Genes to Cells, 10.1111/gtc.12535, 22, 10, 900-917, 2017.10, [URL], Vimentin, desmin, glial fibrillary acidic protein (GFAP) and peripherin belong to type III intermediate filament family and are expressed in mesenchymal cells, skeletal muscle cells, astrocytes and peripheral neurons, respectively. Vimentin and desmin possess N-acetyl-d-glucosamine (GlcNAc)-binding properties on cell surfaces. The rod II domain of these proteins is a GlcNAc-binding site, which also exists in GFAP and peripherin. However, the GlcNAc-binding activities and behaviors of these proteins remain unclear. Here, we characterized the interaction and binding behaviors of these proteins, using various well-defined GlcNAc-bearing polymers synthesized by radical polymerization with a reversible addition-fragmentation chain transfer reagent. The small GlcNAc-bearing polymers strongly interacted with HeLa cells through vimentin expressed on the cell surface and interacted with vimentin-, desmin-, GFAP- and peripherin-transfected vimentin-deficient HeLa cells. These proteins present high affinity to GlcNAc-bearing polymers, as shown by surface plasmon resonance. These results show that type III intermediate filament proteins possess GlcNAc-binding activities on cell surfaces. These findings provide important insights into novel cellular functions and physiological significance of type III intermediate filaments.. |
| 6. | Kim SJ, Ise H, Kim E, Goto M, Akaike T, Chung BH, Imaging and therapy of liver fibrosis using bioreducible polyethylenimine/siRNA complexes conjugated with N-acetylglucosamine as a targeting moiety, Biomaterials, 34, 6504-6514, 2013.09. |
| 7. | Komura K, Ise H, Akaike T, Dynamic behaviors of vimentin induced by interaction with GlcNAc molecules. Glycobiology, Glycobiology, 22, 1741-1759, 2012.12. |
| 8. | Ise H, Goto M, Akaike T, Engulfment and clearance of apoptotic cells based on a GlcNAc-binding lectin-like property of surface vimentin., Glycobiology, 22, 788-805, 2012.06. |
| 9. | Minato A, Ise H, Goto M, Akaike T, Cardiac differentiation of embryonic stem cells by substrate immobilization of insulin-like growth factor binding protein 4 with elastin-like polypeptides, Biomaterials, 33, 515-523, 2012.01. |
| 10. | Kim SJ, Ise H, Goto M, Akaike T, Interactions of vimentin- or desmin-expressing liver cells with N-acetylglucosamine-bearing polymers, Biomaterials, 33, 2154-2164, 2012.03. |
| 11. | Ise M, Ise H, Shiba Y, Kobayashi S, Goto M, Takahashi M,, Akaike T, Ikeda U, Targeting N-acetylglucosamine-bearing polymer-coated liposomes to vascular smooth muscle cells., J Artif Organs., 14, 310-309, 2011.12. |
| 12. | Kim SJ, Ise H, Goto M, Komura K, Cho CS, Akaike T, Gene delivery system based on highly specific recognition of surface-vimentin with N-acetylglucosamine immobilized polyethylenimine., Biomaterials, 32, 3471-3480, 2011.05. |
| 13. | Ise H, Kobayashi S, Goto M, Sato T, Kawakubo M, Takahashi M,, Ikeda U, Akaike T, Vimentin and desmin possess GlcNAc-binding lectin-like properties on cell surfaces, Glycobiology, 20, 843-864, 2010.07. |
| 14. | Kobayashi S, Ise H, Takahashi M, Goto M, Akaike T, Ikeda U, Surface coating of bone marrow cells with N-acetylglucosamine for bone marrow implantation therapy., Biomaterials, 30, 574-582, 2009.02. |
| 15. | Aso S, Ise H, Takahashi M, Kobayashi S, Morimoto H, Izawa A, Goto M, Ikeda U, Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro., J. Control Release, 122, 189-198, 2007.09. |
| 16. | Misawa R, Ise H, Takahashi M, Morimoto H, Kobayashi E, Miyagawa S, Ikeda U, Development of liver regenerative therapy using glycoside-modified bone marrow cells., Biochem Biophys Res Commun., 342, 434-440, 2006.04. |
| 17. | Ise H, Nikaido T, Negishi N, Sugihara N, Suzuki F, Akaike T, Ikeda U, Effective hepatocyte transplantation using rat hepatocytes with low asialoglycoprotein receptor expression. , Am. J. Pathol. , 165, 501-510, 2004.09. |
| 18. | Ise H, Sugihara N, Negishi N, Nikaido T, Akaike T, Low Asialoglycoprotein Receptor Expression as Markers for Highly Proliferative Potential Hepatocytes., Biochem. Biophys. Res. Commun., 285, 172-182, 2001.08. |
| 19. | Ise H, Ferdous A, Sugihara N, Nikaido T, Negishi N, Akaike T, Separation of Mouse Hepatocytes of Distinct Biological Phenotypes Based on Their Asialoglycoprotein Receptor-mediated Binding Affinity to an Artificial Ligand. , Journal of Artificial Organs., 165, 501-510, 1999.07. |
| 20. | Ise H, Takashima S, Nagaoka M, Ferdous A, Akaike T, Analysis of cell viability and differential activity of mouse hepatocytes under 3D and 2D culture in agarose gel., Biotechnology Letters., 21, 209-213, 1999.01. |
| 21. | Nonaka H, Ise H, Sugihara N, Hirose S, Negishi N, Kondo Y, Akaike T, Development of Highly Functional Long-Term Culture Method of Liver Slice Embeded in Polymer Scaffold for Bioartificial Liver., Cell Transplantation , 12, 491-498, 2003.06. |
| 22. | Nagaoka M, Ise H, Akaike T, Immobilized E-cadherin model can enhance cell attachment and differentiation of primary hepatocytes but not proliferation., Biotechnology Letters , 24, 1857-1862, 2002.10. |
| 23. | Hirose S, Ise H, Uchiyama M, Cho CS, Akaike T, Regulation of Asialoglycoprotein Receptor Expression in the Proliferative State of Hepatocytes., Biochem. Biophys. Res. Commun. , 287, 675-681, 2002.10. |
| 24. | Yang J, Goto M, Ise H, Cho CS, Akaike T, Galactosylated alginate as a scaffold for hepatocytes entrapment. , Biomaterials, 23, 471-479, 2002.10. |
| 25. | Kakegawa T, Ise H, Sugihara N, Nikaido T, Negishi N, Akaike T, Tanaka E, Soluble Asialoglycoprotein Receptors Reflect the Apoptosis of Hepatocytes. , Cell Transplantation, 11, 407-415, 2002.09. |
主要総説, 論評, 解説, 書評, 報告書等
| 1. | 伊勢裕彦, 細胞骨格分子ビメンチンの有するGlcNAc結合活性, Trends in Glycoscience and Glycotechnology, 2017.09. |
主要学会発表等
学会活動
学会大会・会議・シンポジウム等における役割
2016.11.21～2016.11.22, バイオマテリアルシンポジウム2017, 座長（Chairmanship）.
2014.11.06～2014.11.06, 第８回 多糖の未来フォーラム, 座長（Chairmanship）.
2016.11.21～2016.11.22, バイオマテリアルシンポジウム2017, 実行委員.
学術論文等の審査
| 年度 | 外国語雑誌査読論文数 | 日本語雑誌査読論文数 | 国際会議録査読論文数 | 国内会議録査読論文数 | 合計 |
|---|---|---|---|---|---|
| 2022年度 | 2 | 2 | |||
| 2021年度 | 3 | 3 | |||
| 2020年度 | 4 | 4 | |||
| 2019年度 | 4 | 4 | |||
| 2018年度 | 5 | 5 | |||
| 2017年度 | 4 | 4 | |||
| 2016年度 | 3 | 3 | |||
| 2015年度 | 3 | 3 | |||
| 2014年度 | 3 | 3 | |||
| 2013年度 | 4 | 4 |
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2022年度～2024年度, 基盤研究(C), 代表, O-GlcNAc化タンパク質の生体修復機構解明とそれに基づいた線維症治療戦略創成.
2019年度～2021年度, 基盤研究(C), 代表, 人工糖鎖高分子を用いた様々な組織線維化の病態機構の解明と標的化技術の創製.
2015年度～2017年度, 基盤研究(C), 代表, 慢性炎症性疾患へのN-アセチルグルコサミン糖鎖高分子を用いた分子標的化技術の創製.
2013年度～2014年度, 基盤研究(S), 分担, 細胞活性化型キメラマトリックスの設計によるＥＳ／ｉＰＳ細胞の機能と分化過程の制御.
競争的資金(受託研究を含む)の採択状況
2023年度～2023年度, 令和5 年度 橋渡し研究プログラム（AMED 課題管理番号：23ym0126816j0002）異分野融合 型研究シーズ（シーズH), 代表, 非アルコール性脂肪肝炎(NASH)誘導肝線維症の改善効果の検討.
2021年度～2021年度, 令和３年度橋渡し研究戦略的推進プログラム シーズA, 代表, N-アセチルグルコサミン糖鎖高分子による組織線維症の予防・改善効果の検討.
寄附金の受入状況
2023年度, ソマール株式会社, N-アセチルグルコサミン糖鎖高分子を用いた線維化改善技術の開発.
2022年度, ソマール株式会社, N-アセチルグルコサミン糖鎖高分子を用いた線維化改善技術の開発.
2021年度, ソマール株式会社, N-アセチルグルコサミン糖鎖高分子を用いた抗炎症作用の検討と線維症に対する治療技術の開発.
2020年度, ソマール株式会社, N-アセチルグルコサミン糖鎖高分子を用いた抗炎症作用の検討と線維症に対する治療技術の開発.
2019年度, ソマール株式会社, ソマール株式会社寄附金/糖鎖高分子を用いた効率的な間葉系幹細胞の単離法の確立.
2018年度, ソマール株式会社, N-アセチルグルコサミン糖鎖高分子を用いた培養材料の開発.
2017年度, ソマール株式会社, N-アセチルグルコサミン糖鎖高分子を用いた培養材料の開発.
2016年度, ソマール株式会社, N-アセチルグルコサミン糖鎖高分子を用いた培養材料の開発.
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