PMID- 23232625
OWN - NLM
STAT- MEDLINE
DCOM- 20130903
LR  - 20211203
IS  - 1573-7209 (Electronic)
IS  - 0969-6970 (Linking)
VI  - 16
IP  - 2
DP  - 2013 Apr
TI  - Sprouty2 expression controls endothelial monolayer integrity and quiescence.
PG  - 455-68
LID - 10.1007/s10456-012-9330-9 [doi]
AB  - Vascular integrity is fundamental to the formation of mature blood vessels and 
      depends on a functional, quiescent endothelial monolayer. However, how 
      endothelial cells enter and maintain quiescence in the presence of angiogenic 
      factors is still poorly understood. Here we identify the fibroblast growth factor 
      (FGF) antagonist Sprouty2 (Spry2) as a key player in mediating endothelial 
      quiescence and barrier integrity in mouse aortic endothelial cells (MAECs): Spry2 
      knockout MAECs show spindle-like shapes and are incapable of forming a 
      functional, impermeable endothelial monolayer in the presence of FGF2. Whereas 
      dense wild type cells exhibit contact inhibition and stop to proliferate, Spry2 
      knockout MAECs remain responsive to FGF2 and continue to proliferate even at high 
      cell densities. Importantly, the anti-proliferative effect of Spry2 is absent in 
      sparsely plated cells. This cell density-dependent Spry2 function correlates with 
      highly increased Spry2 expression in confluent wild type MAECs. Spry2 protein 
      expression is barely detectable in single cells but steadily increases in cells 
      growing to high cell densities, with hypoxia being one contributing factor. At 
      confluence, Spry2 expression correlates with intact cell-cell contacts, whereas 
      disruption of cell-cell contacts by EGTA, TNFalpha and thrombin decreases Spry2 
      protein expression. In confluent cells, high Spry2 levels correlate with 
      decreased extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. In 
      contrast, dense Spry2 knockout MAECs exhibit enhanced signaling by Erk1/2. 
      Moreover, inhibiting Erk1/2 activity in Spry2 knockout cells restores wild type 
      cobblestone monolayer morphology. This study thus reveals a novel Spry2 function, 
      which mediates endothelial contact inhibition and barrier integrity.
FAU - Peier, Martin
AU  - Peier M
AD  - Division of Internal Medicine, University Hospital Zurich, Gloriastrasse 30, 
      GLO30 J14, 8091, Zurich, Switzerland.
FAU - Walpen, Thomas
AU  - Walpen T
FAU - Christofori, Gerhard
AU  - Christofori G
FAU - Battegay, Edouard
AU  - Battegay E
FAU - Humar, Rok
AU  - Humar R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121212
PL  - Germany
TA  - Angiogenesis
JT  - Angiogenesis
JID - 9814575
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DNA Primers)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Spry2 protein, mouse)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - Intracellular Signaling Peptides and Proteins
MH  - Membrane Proteins/*genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Protein Serine-Threonine Kinases
MH  - Real-Time Polymerase Chain Reaction
EDAT- 2012/12/13 06:00
MHDA- 2013/09/04 06:00
CRDT- 2012/12/13 06:00
PHST- 2012/06/22 00:00 [received]
PHST- 2012/12/02 00:00 [accepted]
PHST- 2012/12/13 06:00 [entrez]
PHST- 2012/12/13 06:00 [pubmed]
PHST- 2013/09/04 06:00 [medline]
AID - 10.1007/s10456-012-9330-9 [doi]
PST - ppublish
SO  - Angiogenesis. 2013 Apr;16(2):455-68. doi: 10.1007/s10456-012-9330-9. Epub 2012 
      Dec 12.