The Sphingosine-1-Phosphate Receptor S1PR1 Restricts Sprouting Angiogenesis by Regulating the Interplay between VE-Cadherin and VEGFR2

被引：282

作者：

Gaengel, Konstantin ^{[1
]}

Niaudet, Colin ^{[1
]}

Hagikura, Kazuhiro ^{[1
]}

Siemsen, Barbara Lavina ^{[1
]}

Muhl, Lars ^{[1
]}

Hofmann, Jennifer J. ^{[1
]}

Ebarasi, Lwaki ^{[1
]}

Nystrom, Staffan ^{[2
,3
]}

Rymo, Simin ^{[1
,4
]}

Chen, Long Long ^{[1
]}

Pang, Mei-Fong ^{[1
]}

Jin, Yi ^{[1
]}

Raschperger, Elisabeth ^{[1
]}

Roswall, Pernilla ^{[1
]}

Schulte, Doerte ^{[5
]}

Benedito, Rui ^{[6
,7
]}

Larsson, Jimmy ^{[8
]}

Hellstrom, Mats ^{[8
]}

Fuxe, Jonas ^{[1
]}

Uhlen, Per ^{[2
]}

Adams, Ralf ^{[6
,7
]}

Jakobsson, Lars ^{[1
]}

Majumdar, Arindam ^{[8
]}

Vestweber, Dietmar ^{[5
]}

Uv, Anne ^{[4
]}

Betsholtz, Christer ^{[1
]}

机构：

[1] Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, S-17177 Stockholm, Sweden

[2] Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, S-17177 Stockholm, Sweden

[3] Karolinska Inst, Dept Oncol & Pathol, Canc Ctr Karolinska, S-17177 Stockholm, Sweden

[4] Gothenburg Univ, Inst Biomed, S-41390 Gothenburg, Sweden

[5] Max Planck Inst Mol Biomed, Dept Vasc Cell Biol, D-48149 Munster, Germany

[6] Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany

[7] Univ Munster, D-48149 Munster, Germany

[8] Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden

来源：

DEVELOPMENTAL CELL | 2012年 / 23卷 / 03期

基金：

瑞典研究理事会;

关键词：

ENDOTHELIAL GROWTH-FACTOR; PROTEIN-COUPLED RECEPTOR; VASCULAR DEVELOPMENT; PDGF-B; SPHINGOSINE; 1-PHOSPHATE; LYMPHOCYTE EGRESS; CELLS; MICE; BLOOD; BETA;

D O I：

10.1016/j.devcel.2012.08.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Angiogenesis, the process by which new blood vessels arise from preexisting ones, is critical for embryonic development and is an integral part of many disease processes. Recent studies have provided detailed information on how angiogenic sprouts initiate, elongate, and branch, but less is known about how these processes cease. Here, we show that S1PR1, a receptor for the blood-borne bioactive lipid sphingosine-1-phosphate (S1P), is critical for inhibition of angiogenesis and acquisition of vascular stability. Loss of S1PR1 leads to increased endothelial cell sprouting and the formation of ectopic vessel branches. Conversely, S1PR1 signaling inhibits angiogenic sprouting and enhances cell-to-cell adhesion. This correlates with inhibition of vascular endothelial growth factor-A (VEGF-A)-induced signaling and stabilization of vascular endothelial (VE)-cadherin localization at endothelial junctions. Our data suggest that S1PR1 signaling acts as a vascular-intrinsic stabilization mechanism, protecting developing blood vessels against aberrant angiogenic responses.

引用

页码：587 / 599

页数：13

共 45 条

[1]

VE-Cadherin-Mediated Cell-Cell Interaction Suppresses Sprouting via Signaling to MLC2 Phosphorylation [J].