Lymphangiogenesis during liver repair after acute liver injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kitasato University
• Principal Investigator: ITO YOSHIYA 北里大学, 医学部, 准教授 (40203187)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝修復 / リンパ管

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.

Free Research Field

消化器

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。