دورية أكاديمية
أعرض في EDS

The transcription factor ERG regulates a low shear stress-induced anti-thrombotic pathway in the microvasculature.

التفاصيل البيبلوغرافية
العنوان: The transcription factor ERG regulates a low shear stress-induced anti-thrombotic pathway in the microvasculature.
المؤلفون: Peghaire C; National Heart and Lung Institute, Imperial College London, London, UK., Dufton NP; National Heart and Lung Institute, Imperial College London, London, UK., Lang M; National Heart and Lung Institute, Imperial College London, London, UK., Salles-Crawley II; Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK., Ahnström J; Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK., Kalna V; National Heart and Lung Institute, Imperial College London, London, UK., Raimondi C; National Heart and Lung Institute, Imperial College London, London, UK., Pericleous C; National Heart and Lung Institute, Imperial College London, London, UK., Inuabasi L; National Heart and Lung Institute, Imperial College London, London, UK., Kiseleva R; Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, USA., Muzykantov VR; Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, USA., Mason JC; National Heart and Lung Institute, Imperial College London, London, UK., Birdsey GM; National Heart and Lung Institute, Imperial College London, London, UK., Randi AM; National Heart and Lung Institute, Imperial College London, London, UK. a.randi@imperial.ac.uk.
المصدر: Nature communications [Nat Commun] 2019 Nov 01; Vol. 10 (1), pp. 5014. Date of Electronic Publication: 2019 Nov 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Gene Expression Regulation*, Microvessels/*metabolism , Thrombomodulin/*metabolism , Thrombosis/*metabolism , Transcriptional Regulator ERG/*metabolism, Animals ; Cells, Cultured ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Humans ; Kruppel-Like Transcription Factors ; Mice, Knockout ; Microvessels/cytology ; Promoter Regions, Genetic/genetics ; Signal Transduction/genetics ; Stress, Mechanical ; Thrombomodulin/genetics ; Thrombosis/genetics ; Transcriptional Regulator ERG/genetics
مستخلص: 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 (Erg iEC-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 Erg iEC-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.
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معلومات مُعتمدة: FS/16/22/32045 United Kingdom BHF_ British Heart Foundation; PG/17/42/33039 United Kingdom BHF_ British Heart Foundation; RG/18/3/33405 United Kingdom BHF_ British Heart Foundation; R01 HL128398 United States HL NHLBI NIH HHS; FS/12/60/29874 United Kingdom BHF_ British Heart Foundation; PG/17/22/32868 United Kingdom BHF_ British Heart Foundation; PG/14/90/31219 United Kingdom BHF_ British Heart Foundation; T32 HL007971 United States HL NHLBI NIH HHS; 21223 United Kingdom VAC_ Versus Arthritis
المشرفين على المادة: 0 (Klf2 protein, mouse)
0 (Kruppel-Like Transcription Factors)
0 (Thrombomodulin)
0 (Transcriptional Regulator ERG)
تواريخ الأحداث: Date Created: 20191103 Date Completed: 20200316 Latest Revision: 20240421
رمز التحديث: 20240421
مُعرف محوري في PubMed: PMC6825134
DOI: 10.1038/s41467-019-12897-w
PMID: 31676784
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-019-12897-w