The human body is known for its ability to heal itself. Even after two-thirds of its mass has been removed, it can still grow again. The liver can fail due to damage from drugs, alcohol, or obese people.
There is only one effective treatment for end-stage liver disease.
There is no shortage of organs for transplant. It can take over five years for a patient to receive a transplant in the US. Only a small number of patients on the waiting list received a transplant in the next few years.
Wouldn't it be great if there was a drug that could help the body heal itself?
I am the founding director of the Pittsburgh Liver Research Center and run a lab that studies cancer and regeneration of the bile duct. In our recently published research, my team and I found that if you use a new medication, it can help speed up the regeneration and repair of damaged organs in mice.
The liver performs over 500 functions in your body, including breaking down toxins like ammonia and converting excess sugar into glycogen for storage.
Hepatocytes take on these many tasks by dividing and conquering. Cells are directed to perform specialized functions by turning on specific genes in each zone after being separated from the rest of the body.
The expression of these genes has not been understood.
Over the past two decades, my team and other labs have identified a group of 19 Wnts that play an important role in controlling liver function and regeneration.
Researchers know that Wnt is involved in the repair process in damaged liver cells, but they don't know which Wnt is involved in regeneration and which is located in the liver.
My team and I used a new technology calledmolecular cartography to identify how strongly and where 100 liver function genes are active.
Two of the 19 Wnt genes, Wnt2 and Wnt9b, are functional in the liver. We found that Wnt2 and Wnt9b were located in the cells that line the blood vessels in the area that plays a role in metabolism.
The elimination of the two Wnt genes resulted in all the cells in the body expressing only genes that are limited to zone 1.
According to this finding, Wnt is the master Regulator of the process of gene activation that can modify their functions.
Eliminating the two Wnt genes from the cells completely stopped the regeneration of the cells after they were removed from the body.
We decided to test a new drug to see if it worked. Similar functions with Wnt are shared by this drug.
This drug was given to mice that were genetically engineered to lack Wnt2 and Wnt9b. The drug was able to fully recover the functions of the cells.
We wanted to find out how well this drug worked to repair the body after an overdose. Over-the-counter medication known as tylenol is used to treat pain and achy joints.
An overdose of the drug can cause serious damage to the body. It can lead to death if it isn't treated immediately. It's one of the most common causes of severe injury that requires a transplant in the US.
There is only one medication that can be used to treat it, and only if it is taken immediately after an overdose.
The new drug was tested on mice that had been exposed to toxic levels of Tylenol. We found that one dose was able to decrease the amount of inflammation in the body.
The findings show that tissue regeneration is happening.
Improving treatments for bile duct diseases is one way to address the shortage of transplants. Current medications can cure the disease, but other diseases have not seen the same progress.
Many patients end up needing a transplant due to the fact that very few effective treatments are available for the diseases.
The need for transplantation could be circumvented if the liver's ability to repair itself was improved. There is a need for further study of drugs that promote regeneration.
Satdarshan Monga is a professor at the University of Pittsburgh.
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