Role of VEGFR1 signaling in mucosal repair after ulcerative colitis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16968
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kitasato University
• Principal Investigator: BETTO TOMOHIRO 北里大学, 医学部, 助教 (40623202)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 潰瘍性大腸炎 / VEGF / Treg

Outline of Final Research Achievements

The present study was to examine the role of VEGFR1 signaling in the colonic mucosal repair in a mouse model of ulcerative colitis. The mucosal repair in DSS-induced colitis was dependent on VEGFR1 signaling. The repair was induced by accumulation of VEGFR1+/CXCR4+ Tregs in the injured regions, promoting angiogenesis by producing TGF beta. The accumulation of Tregs was mediated by SDF-1/CXCR4 pathway. These results suggest that VEGFR1 signaling may be a potential therapeutic target to alleviate ulcerative colitis and promote mucosal repair.

Free Research Field

消化器

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎の粘膜修復制御機構はこれまで十分理解されていなかった。本研究ではVEGFR1シグナルがSDF-1/CXCR4経路を介してTreg集積を誘導し、血管新生を促進することで粘膜修復を増強するという新規のメカニズムを明らかにすることができた。TregにおけるVEGFFR1シグナル活性化を標的とした新しい潰瘍性大腸炎寛解療法に結びつく可能性が期待される。