October 29, 2022: The liver is known for regenerating itself, but there are exceptions. Damage from medications and alcohol can cause liver failure, and transplantation is the only effective treatment for it.
Liver transplantation is costly, and availability does not match demand. A good alternative is liver regeneration through drug infusion, according to Dr Satdarshan Paul Singh Moga, Professor of Pathology and Medicine, University of Pittsburgh Health Sciences and founding director of the Pittsburgh Liver Research Center.
Dr Moga and his team have been studying liver regeneration and cancer for the past two decades. Their research has led them to find an answer to what could help in liver repair and cell regeneration, thereby possibly cutting down the need for liver transplantation. They say activating a protein in the liver with medication helps in the regeneration and repair of the liver.
Liver performs many functions, from producing protein that carries fat to controlling blood glucose levels. Liver cells perform certain functions directed by genes in three main zones of the liver. But what controls these gene activations is not fully known.
Role of Wnts in liver function
Dr Moga’s team and other labs over the years have identified one group of 19 proteins called Wnts that play an important role in controlling liver function and regeneration. The team used molecular cartography to identify how these genes activate a particular function in the liver. They found only Wnt2 and Wnt9b from the Wnts family present in the liver. These were located in the endothelial cells lining the blood vessels in zone 3 of the liver.
The team found that eliminating these two Wnt genes from endothelial cells completely stopped liver cell division, and thus regeneration, after partial surgical removal of the liver in the mice.
To further test this theory, genetically engineered mice with no Wnt2 and Wnt9b genes were given a drug, an antibody called FL6.13, with similar functions to Wnt proteins. The drug took on the function of the two genes and was able to completely recover liver cell division and repair functions.
The team then tested the theory with Tylenol. Tylenol poisoning can cause severe liver injury requiring liver transplantation. Mice were overdosed with Tylenol, and their impaired liver function was treated with the new drug. According to Dr Moga, one drug dose was able to decrease liver injury biomarkers – proteins the liver releases when injured – in the blood and reduce liver tissue death.
These findings can be groundbreaking in finding a cure for liver damage that cannot be treated. The new drug is an indicator that liver cells can repair and regenerate.