| Project/Area Number |
18K19553
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
Kubota Yoshiaki 慶應義塾大学, 医学部(信濃町), 教授 (50348687)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
馬場 理也 熊本大学, 国際先端医学研究機構, 准教授 (10347304)
|
|---|
| Project Period (FY) |
2018-06-29 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| Keywords | 血管 / リンパ管 / Prox1 / マウス / 発生 / がん |
|---|
| Outline of Final Research Achievements |
Vascular and lymphatic systems are two major circulatory systems properly distributed throughout the body. The structures of these two are histologically very similar but anatomically never share the lumen with except for the “venous angle”, the final junction of collecting lymph ducts and subclavian veins. The expression of Prospero Homeobox Protein 1 (Prox1), a master transcription factor of lymphatic specification from venous endothelial cells, determines both the initiation and maintenance of the identity as lymphatic endothelial cells, somehow contributing to the separation of blood and lymphatic systems. Here, using genetically modified mice, we found a tumor suppressor, which pathway ultimately governs the expressions of Prox1, and developmentally separates blood and lymphatic vascular systems. Our data may pave the way to treat the secondary lymphedema, which frequently occurs after extensive lymph node dissection associated with cancer surgery.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は血管・リンパ管という体内の2つの酷似する循環系が、なぜ一切交通することなく、独立したネットワークを形成するのかという、長年世界的に未解明とされている生物学的な疑問を解き明かしたという学術的重要性を持つ。また、臨床的側面からは、リンパ浮腫の病態解明、治療への発展性を秘める。将来的には本研究で見出されたシグナル経路に介入することで、局所で薬剤的に静脈－リンパ管シャントを創出できれば、リンパ浮腫の画期的治療になると考える。
|
