@article{Dufton:2017:10.1038/s41467-017-01169-0,
author = {Dufton, NP and peghaire, CR and Osuna-Almagro, L and Raimondi, C and Kalna, V and Chuahan, A and Webb, G and Yang, Y and Birdsey, GM and Lalor, P and Mason, JC and Adams, D and Randi, AM},
doi = {10.1038/s41467-017-01169-0},
journal = {Nature Communications},
pages = {1--14},
title = {Dynamic regulation of canonical TGFβ signaling by endothelial transcription factor ERG protects from liver fibrogenesis},
url = {http://dx.doi.org/10.1038/s41467-017-01169-0},
volume = {8},
year = {2017}
}

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TY  - JOUR
AB  - The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (ErgcEC-Het) and inducible homozygous deficient mice (ErgiEC-KO), in a SMAD3-dependent manner. Acute administration of the TNF-α inhibitor etanercept inhibits carbon tetrachloride (CCL4)-induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression also correlates with EndMT in tissues from patients with end-stage liver fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG represents a promising candidate biomarker for assessing EndMT in liver disease.
AU  - Dufton,NP
AU  - peghaire,CR
AU  - Osuna-Almagro,L
AU  - Raimondi,C
AU  - Kalna,V
AU  - Chuahan,A
AU  - Webb,G
AU  - Yang,Y
AU  - Birdsey,GM
AU  - Lalor,P
AU  - Mason,JC
AU  - Adams,D
AU  - Randi,AM
DO  - 10.1038/s41467-017-01169-0
EP  - 14
PY  - 2017///
SN  - 2041-1723
SP  - 1
TI  - Dynamic regulation of canonical TGFβ signaling by endothelial transcription factor ERG protects from liver fibrogenesis
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-017-01169-0
UR  - https://www.nature.com/articles/s41467-017-01169-0
UR  - http://hdl.handle.net/10044/1/50493
VL  - 8
ER  - 

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