Citation

BibTex format

@article{Peghaire:2019:10.1038/s41467-019-12897-w,
author = {Peghaire, C and Dufton, N and Lang, M and Salles, I and Ahnstroem, J and Kalna, V and Raimondi, C and Pericleous, C and Inuabasi, L and Kiseleva, R and Muzykantov, V and Mason, J and Birdsey, G and Randi, A},
doi = {10.1038/s41467-019-12897-w},
journal = {Nature Communications},
title = {The transcription factor ERG regulates a low shear stress-induced anti-thrombotic pathway in the microvasculature},
url = {http://dx.doi.org/10.1038/s41467-019-12897-w},
volume = {10},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Endothelial cells actively maintain an anti-thrombotic environment; loss of this protective function may lead to thrombosis and systemic coagulopathy. The transcription factor ERG is essential to maintain endothelial homeostasis. Here we show that inducible endothelial ERG deletion (ErgiEC-KO) in mice is associated with spontaneous thrombosis, hemorrhages and systemic coagulopathy. We find that ERG drives transcription of the anti-coagulant thrombomodulin (TM), as shown by reporter assays and chromatin immunoprecipitation. TM expression is regulated by shear stress (SS) via Krüppel-like factor 2 (KLF2). In vitro, ERG regulates TM expression under low SS conditions, by facilitating KLF2 binding to the TM promoter. However, ERG is dispensable for TM expression in high SS conditions. In ErgiEC-KO mice, TM expression is decreased in liver and lung microvasculature exposed to low SS but not in blood vessels exposed to high SS. Our study identifies an endogenous, vascular bed- specific anti-coagulant pathway in microvasculature exposed to low SS.
AU - Peghaire,C
AU - Dufton,N
AU - Lang,M
AU - Salles,I
AU - Ahnstroem,J
AU - Kalna,V
AU - Raimondi,C
AU - Pericleous,C
AU - Inuabasi,L
AU - Kiseleva,R
AU - Muzykantov,V
AU - Mason,J
AU - Birdsey,G
AU - Randi,A
DO - 10.1038/s41467-019-12897-w
PY - 2019///
SN - 2041-1723
TI - The transcription factor ERG regulates a low shear stress-induced anti-thrombotic pathway in the microvasculature
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-019-12897-w
UR - http://hdl.handle.net/10044/1/74316
VL - 10
ER -