Lipid mediators regulate inflammatory bowel diseases via lymphangiogenesis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17702
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kitasato University
• Principal Investigator: KOJO KEN 北里大学, 医学部, 助教 (20525414)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 炎症性腸疾患 / プロスタグランジン / リンパ管新生

Outline of Final Research Achievements

Using a model of ulcerative colitis, we investigated underlying mechanisms by which lymphangiogenesis is involved in tissue repair after acute intestinal inflammation. Administration of a lymphatic endothelial receptor VEGFR3 inhibitor exacerbated colitis as well as suppressed lymphangiogenesis. Prostaglandin E2 (PGE2) receptor subtype EP4 signaling promoted inflammatory resolution and tissue repair by enhancing drainage function through the formation of new and expanded lymphatic vessels by accumulating macrophages. Our results suggest that activation of EP4 receptor signaling during the repair phase of ulcerative colitis may lead to treatment of ulcerative colitis remission induction.

Free Research Field

消化器

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患を制御するには炎症だけでなく、粘膜修復も考慮しなければならないことが本研究からみえてきた。この修復には新生リンパ管形成とそのドレナージ機能を活用することが重要である。本研究において、炎症性腸疾患における組織修復においてリンパ管新生の果たす意義と制御機構の解明が寛解導入治療につながる可能性がある。