Role of VEGFR1 signaling in lymphangiogenesis during endometriosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18704
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kitasato University
• Principal Investigator: Sekiguchi Kazuki 北里大学, 医学部, 助教 (90458810)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 子宮内膜症 / リンパ管

Outline of Final Research Achievements

In the present study, we examined whether lymphangiogenesis as well as angiogenesis contributes to the development of endometriosis using ectopic endometriosis model in mice. Inhibition with VEGFR3 signaling suppressed lymphatic vessel density and the size of endometriotic implants. In VEGFR1 deficient mice, lymphangiogenesis as indicated by lymphatic vessel density, lymphatic growth factors, and lymphatic endothelial markers were decreased as compared with those in wild-type mice. Lymphatic growth factors secreted from accumulated macrophages and fibroblasts in the endometrial implants were involved in the progression of endometriosis in a VEGFR1 signaling dependent manner.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

生殖年齢の女性のQOLを損なう子宮内膜症には有効な治療法が望まれている。本研究によって、子宮内膜病変の間質に集積するマクロファージや線維芽細胞がリンパ管新生を増強することで子宮内膜症進展を促進することを明らかにした。これまでリンパ管新生の子宮内膜症における役割は不明であったことから、ひとつのメカニズムを解明できたものと考えられる。今後、子宮内膜症への治療的応用につながるものと期待される。