ERG protects against liver disease
A team composed of researchers from Imperial College London and the University of Birmingham has demonstrated a protective role of the endothelial transcription factor ETS-related gene (ERG) in the liver.
Described online in Nature Communications on 12 October 2017, their results show that ERG helps maintain the unique properties of the endothelial cells that line the inside of the small blood vessels in the liver, while ERG deletion results in the endothelial-to-mesenchymal transition (EndoMT, or EndMT) and contributes to tissue inflammation and fibrosis associated with liver disease.
The researchers believed that ERG represents a potential biomarker for evaluating the health of blood vessels and liver tissue.
Liver disease is one of the most frequent causes of death worldwide, and its incidence is increasing year-on-year. Unfortunately, the symptoms usually do not appear until the liver disease is advanced. It is highly necessary to identify new biomarkers that could enable earlier diagnosis of liver disease.
Some scientists in this field put their eyes on the small blood vessels within the liver. The liver receives the oxygen and nutrients it needs in blood. The blood supply depends on endothelial cells, which form the linings of the blood vessels, or called the endothelium. Endothelial cells are involved in many important functions, such as barrier function, blood clotting, and inflammation.
Recent studies have shown that the transcriptional regulator ERG
is required for the differentiation of endothelial cells from precursor cells. In this work, the researchers found that loss of ERG in vitro and in vivo results in the EndoMT, a complex biological process in which endothelial cells lose their specific markers. There is evidence that the EndoMT correlates with tissue inflammation and fibrotic disorders.
The researchers carried out an extensive set of experiments in human endothelial cells, human liver tissues, and mouse models. Transcriptome analysis of ERG-deficient human endothelial cells revealed dysregulation of genes involved in SMAD1
and SMAD2/3 signalling. Mice lacking endothelial ERG expression exhibited EndoMT and liver fibrogenesis. Reduced ERG expression was also associated with EndoMT in tissue samples from liver disease patients.
Collectively, these data demonstrate that ERG deficiency leads to EndoMT and liver fibrogenesis, suggesting that ERG prevents against liver disease. ERG might be used as a biomarker to evaluate the health of the liver.