Blood Vessel ‘Master Gene’ Discovery Could Lead to Treatments for Liver Disease

Source: Imperial College London

Summary: Researchers have identified a key gene in blood vessels which can offer a new way to potentially treat liver disease.

Liver disease is one of the biggest cause of death and there is an increase in cases over the last decade. A quarter of the liver diseases are related to alcohol drinking. Many patients do not show any symptoms until there is an irreparable damage of liver, where liver transplantation is the only option. Researchers at Imperial College London, Birmingham identified a ‘master gene’ which helps in maintaining the health of blood vessels and their inner lining of specialized cells called the endothelium. Endothelial cells play an important role in the inflammatory response and enable white blood cells to move in and out of the bloodstream. The findings were published in the journal Nature Communications.

ETS Related Gene

Blood vessels play a key role in liver disease: The hepatic vein (centre) is surrounded by sinusoidal (red) blood vessels. Credit: Imperial College London

In this study, researchers have found that when the ERG master gene expression is inhibited, the endothelial cells became dysfunctional and reverted back to an undifferentiated state through a process called endothelial-mesenchymal transition (EndoMT). This EndoMT is associated with inflammation of the tissues and build up of fibrotic tissue, a sign of liver disease. A similar process is observed in animals, a loss of ERG gene function was liked with liver injury. According to this study, it shows ERG can be potentially used as a biomarker to monitor the health of blood vessels.

Professor Anna Randi, the leader of the research, said, “The study shows how acute and chronic inflammation can dramatically affect the activity of this master gene which is essential for endothelial cells function, with profound consequences not only for the vasculature but also for the surrounding tissue function, which leads to liver damage. This is an exciting finding, as it opens a new way to prevent or treat liver disease by targeting the endothelium”, further added, “We plan to study whether patients with heart disease and fibrosis also have a loss of ERG in their blood vessels, and how we might possibly exploit this pathway for the treatment of these patients.”

More Information: Neil P. Dufton et al, “Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis”, Nature Communications (2017). DOI: 10.1038/s41467-017-01169-0

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