2010 Fiscal Year Final Research Report
Inhibition of an endothelial cell surface molecule by its internalization.
| Project/Area Number |
20590399
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
NARAZAKI Masashi Osaka University, 大学院・医学研究科, 助教 (00467573)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANAKA Toshio 大阪大学, 大学院・医学系研究科, 准教授 (40273651)
OGATA Atsushi 大阪大学, 大学院・医学系研究科, 助教 (90309451)
|
|---|
| Research Collaborator |
TOSATO Giovanna NATIONAL INSTITUTE OF HEALTH, USA, NATIONAL CANCER INSTITUTE, PRINCIPAL INVESTIGATOR
SEGARRA Marta NATIONAL INSTITUTE OF HEALTH, USA, NATIONAL CANCER INSTITUTE, FELLOW
HOU Xu NATIONAL INSTITUTE OF HEALTH, USA, NATIONAL EYE INSTITUTE, FELLOW
LI Xuri NATIONAL INSTITUTE OF HEALTH, USA, NATIONAL EYE INSTITUTE, PRINCIPAL INVESTIGATOR
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Keywords | 血管新生 / 受容体 / 発現制御 / 血管内皮細胞 / Neuropilin / 内在化 / 薬理学 |
|---|
| Research Abstract |
Neuropilin-1 (NRP1) is the cell surface receptor shared by Sema3A and VEGF_<165>. We showed that certain scavenger receptor ligands, sulfated polysaccharides including dextran sulfate, fucoidan, poly(G) and oligo G, induced internalization of endothelial cell-surface of NRP1 and blocked the binding and in vitro function of Sema3A and VEGF_<165>. Polysaccharides, poly or oligo (A), (T), (C) did not share this property. Administration of fucoidan or oligo G to mice reduced VEGF_<165>-induced angiogenesis in vivo. These results identify certain sulfated polysaccharides and oligo G as inducers of internalization and functional inhibition of NRPI, and provide poof-of-principle that engineered receptor internalization is an effective strategy for reducing levels and function of cell-surface receptors.
|
