Potential new target for treatment of Liver Disease

CRM researchers have discovered a potential new target for the treatment of a type of liver disease that affects the bile ducts. 

A new paper published today in Nature Communications has revealed that blocking a particular cellular process in the bile duct can reverse liver damage in mice.

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Whilst a healthy bile duct is critical for normal digestion, damage to this vessel over time can produce serious scarring and liver failure. There are few effective treatments for biliary diseases which account for around 16% of liver transplants.

Normally, the bile duct is able to repair itself but Dr Sofia Ferreira-Gonzalez, Professor Stuart Forbes and colleagues have found that a process called senescence can prevent this self-repair, leading to biliary disease. Senescence is when cells stop dividing and it is important in preventing tumour growth. However, the research team have shown that senescent cells prevent bile ducts regenerating following damage.

Experiments indicate that senescent bile duct cells are able to produce molecular signals, such as Transforming Growth Factor β (TGF β), which also cause nearby cells to become senescent. By blocking TGFβ in animal models of biliary disease, they found that the injury was significantly reduced.

Professor Stuart Forbes, Director of the MRC Centre for Regenerative Medicine who led the study said,

The causes of biliary disease are poorly understood which has hampered the development of effective treatments. This work will help us to identify rational targets for treatment

This work was funded by the Medical Research Council and published in Nature Communications https://www.nature.com/articles/s41467-018-03299-5 

Nature Communications, volume 9, Article number: 1020 (2018) doi:10.1038/s41467-018-03299-5

Story by Katie Ember, 09 March 2018