28/10/2020

Our liver has a remarkable capacity to regenerate. However, the molecular mechanisms behind this ability are not yet entirely clear. Now, a team led by Georg Halder (VIB-KU Leuven Center for Cancer Biology) elucidates an indirect role for the bile ducts in liver regeneration. The results appear in Gastroenterology.

The power of the liver

The liver has a reputation for helping our body get rid of toxins, but the organ is equally impressive for its regenerative capacities. Unfortunately, the liver's ability to heal itself can be impaired by disease and age.

How the liver works its regenerative magic, however, is still somewhat of a mystery. The Hippo pathway – a sequence of molecular steps – is regarded as a major regulator of organ growth and regeneration. YAP and TAZ are two proteins in that pathway which can drive growth, but previous studies on their role during regeneration are ambiguous.

YAP, TAZ, and bile ducts

Work by the lab of Georg Halder (VIB-KU Leuven Center for Cancer Biology) and colleagues now show that the role of YAP and TAZ is indirect and occurs via influencing the bile ducts.

Georg Halder explains: "We investigated regeneration after toxic injury in the liver of mice. Unexpectedly, we found that Yap/Taz deletion in liver cells did not impact liver regeneration, but deletion in cells of the bile ducts did. The effects on the bile ducts had a knock-on effect on the capacity of the liver to regenerate."

 

More specifically, Yap/Taz mutant bile ducts degenerated, which blocked the flow of bile. This stalled the removal of cellular waste products from the sites of injury. These experiments show how liver disease can negatively impact the regenerative ability of the liver.

Georg Halder says: "Understanding mechanisms that impair liver regeneration may ultimately enable us to develop new therapies that prompt the liver, and possibly other organs, to regain and enhance their ability to regenerate."

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