Peghaire, C;
Dufton, NP;
Lang, M;
Salles-Crawley, II;
Ahnström, J;
Kalna, V;
Raimondi, C;
Pericleous, C;
Inuabasi, L;
Kiseleva, R;
et al.
Peghaire, C; Dufton, NP; Lang, M; Salles-Crawley, II; Ahnström, J; Kalna, V; Raimondi, C; Pericleous, C; Inuabasi, L; Kiseleva, R; Muzykantov, VR; Mason, JC; Birdsey, GM; Randi, AM
(2019)
The transcription factor ERG regulates a low shear stress-induced anti-thrombotic pathway in the microvasculature.
Nat Commun, 10 (1).
p. 5014.
ISSN 2041-1723
https://doi.org/10.1038/s41467-019-12897-w
SGUL Authors: Salles-Crawley, Isabelle Irene
Abstract
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 anticoagulant 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 anticoagulant pathway in microvasculature exposed to low SS.
Item Type: |
Article
|
Additional Information: |
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2019 |
Keywords: |
Animals, Cells, Cultured, Endothelial Cells, Gene Expression Regulation, Humans, Kruppel-Like Transcription Factors, Mice, Knockout, Microvessels, Promoter Regions, Genetic, Signal Transduction, Stress, Mechanical, Thrombomodulin, Thrombosis, Transcriptional Regulator ERG, Cells, Cultured, Endothelial Cells, Animals, Mice, Knockout, Humans, Thrombosis, Thrombomodulin, Signal Transduction, Gene Expression Regulation, Stress, Mechanical, Kruppel-Like Transcription Factors, Promoter Regions, Genetic, Microvessels, Transcriptional Regulator ERG, MD Multidisciplinary |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Nat Commun |
ISSN: |
2041-1723 |
Language: |
eng |
Dates: |
Date | Event |
---|
1 November 2019 | Published | 30 September 2019 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
31676784 |
Web of Science ID: |
WOS:000493712700007 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/113735 |
Publisher's version: |
https://doi.org/10.1038/s41467-019-12897-w |
Statistics
Item downloaded times since 07 Oct 2021.
Actions (login required)
![Edit Item](/style/images/action_view.png) |
Edit Item |