Lymphangiogenesis during liver repair after acute liver injury
| Project/Area Number |
19K09156
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Kitasato University |
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Principal Investigator |
ITO YOSHIYA 北里大学, 医学部, 准教授 (40203187)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 肝修復 / リンパ管 / 肝臓 / 虚血再灌流 / 肝 / 修復 / プロスタグランジン |
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| Outline of Research at the Start |
本研究では、マウス肝虚血再潅流障害モデルを用いて、肝障害後のリンパ管新生が肝修復にはたす役割と、その制御機構に生理活性脂質プロスタグランジンE受容体シグナルが関与することを明らかにすることを目的とする。研究成果を基にして、生理活性脂質シグナルによるリンパ管新生作用を基軸とした肝修復の治療的意義を検討し、新規肝再生治療応用や創薬開発の可能性を探る。
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| Outline of Final Research Achievements |
Using a mouse model of hepatic ischemia/reperfusion (I/R) injury, we investigated hepatic lymphatic structure, growth, and function. Hepatic I/R injury enhanced lymphangiogenesis around the portal tract and this was associated with increased expression of pro-lymphangiogenic growth factors including VEGF-C and VEGF-D. Recombinant VEGF-D treatment facilitated liver repair in association with the expansion of lymphatic vessels and increased gene expression related to the reparative macrophage phenotype. Treatment with a VEGFR3 inhibitor suppressed liver repair, lymphangiogenesis, drainage function, and accumulation of VEGFR3-expressing reparative macrophages. VEGF-C and VEGF-D upregulated gene expression related to lymphangiogenic factors and the reparative macrophage phenotype in cultured macrophages. These results suggest that activation of VEGFR3 signaling promotes lymphangiogenesis and reparative macrophages, both of which play roles in liver repair.
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| Academic Significance and Societal Importance of the Research Achievements |
肝障害後の肝組織修復が障害されると肝不全に至り患者予後は不良となる。これまで肝リンパ管が肝組織修復に関与することは未解明であったが、本研究において、新生するリンパ管の役割とその分子制御機構が明らかになった。肝リンパ管新生を制御するメカニズムをさらに明らかにすることにより。各種の肝病態を改善する治療法の開発に可能性がある。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Activation of iNKT Cells Facilitates Liver Repair After Hepatic Ischemia Reperfusion Injury Through Acceleration of Macrophage Polarization.2021
Author(s)
Goto T, Ito Y, Satoh M, Nakamoto S, Nishizawa N, Hosono K, Naitoh T, Eshima K, Iwabuchi K, Hiki N, Amano H.
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Journal Title
Front Immunol.
Volume: 12
Pages: 754106-754106
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Roles of Thromboxane Receptor Signaling in Enhancement of Lipopolysaccharide-Induced Lymphangiogenesis and Lymphatic Drainage Function in Diaphragm.2021
Author(s)
Matsuda H, Ito Y, Hosono K, Tsuru S, Inoue T, Nakamoto S, Kurashige C, Hirashima M, Narumiya S, Okamoto H, Majima M.
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Journal Title
Arterioscler Thromb Vasc Biol.
Volume: 41
Issue: 4
Pages: 1390-1407
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Thromboxane A(2) receptor signaling in endothelial cells attenuates monocrotaline-induced liver injury.2019
Author(s)
Otaka F, Ito Y, Inoue T, Ohkubo H, Nishizawa N, Kojo K, Betto T, Yamane S, Narumiya S, Koizumi W, Majima M
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Journal Title
Toxicol Appl Pharmacol
Volume: 381
Pages: 114733-114733
DOI
Related Report
Peer Reviewed / Open Access
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