The liver is well-known for its ability to produce liver. Regeneration ability. Even after the removal of two-thirds, the liver can fully regrow. However, liver damage due to medications, alcohol abuse or obesity could eventually lead to its death.
The only treatment available for end-stage liver disease at this time is Transplantation.
There is however, a Insufficient organsTransplantation. Patients may be required to You can wait between 30 days and 5 yearsA liver transplant can be done in the United States. One of the over 11,600 patientsOnly a little more than 9,200 people were on the waiting list for a transplant of the liver in 2021.
What if there was a drug that could help the body regenerate its liver instead of liver transplantation?
I am the founder and director of the Pittsburgh Liver Research CenterRun a lab Study of liver regeneration and cancer. Our Recently published researchMy team and I discovered that activating a specific protein with a new medication can accelerate the process of repair and regeneration after liver injury in severe cases or partial surgical removal in mice.
Key players in liver regeneration
The liver is a vital organ. Over 500 functionsYour body IncludedProducing proteins that transport fat through the body, converting excess sugar into glycogen for storage and breaking down toxins such as ammonia.
Hepatocytes or liver cells take on these tasks using a divide and conquer strategy also known as zonation. This division of the liver in three different zones allows cells to be directed to perform specialized functions. Cells are activated by specific genes within each zone.
It is not clear what exactly controls their expression.
Over the last two decades, my lab and other labs identified a single group of 19 proteins. WntsThese factors play an important role when it comes to liver function and regeneration.
Researchers know that Wnt proteins activate the repair process of damaged liver cells. However, it is still a mystery which Wnt proteins control zonation or regeneration.
My team and i used a new technology called “Identify” to find these proteins and their origins. molecular cartographyFind out where and how strong 100 genes governing liver function are active.
We found that Only two genes from the 19 Wnt family are availableWnt2b and Wnt9b were both functionally present within the liver. Also, Wnt2b and Wnt9b were found in the endothelial cells that line the blood vessels in Zone 3 of the liver. This area plays an important role in many metabolic functions.
We were surprised to discover that all liver cells expressed only genes normally restricted to zone 1 and this significantly limited the liver’s overall function.
This indicates that liver cells undergo an ongoing push and draw in gene activation that can modify the functions of their function, and that Wnt is the master regulator.
After partial surgery to remove the liver, the Wnt genes were removed from the endothelial cells. This also stopped cell division and regeneration.
Liver regeneration after Tylenol overdose
Then, we decided to Test to see if a new drug is safeCould help with liver regeneration and zonation. This drug is an AntibodyFL6.13, also known as FL6.13, has similar functions to Wnt protein, activating liver regeneration.
Two days later, we gave the drug to mice that had been genetically engineered to be devoid of Wnt2b and Wnt9b. The drug was capable of almost completely restoring liver cell division and repair functions.
Finally, we wanted the drug to be able to restore liver function after Tylenol abuse. Tylenol or Acetaminophen is an over the counter medication used to treat many conditions. FièvrePain.
Tylenol overdose can lead to serious side effects. cause severe liver damage. It can cause liver failure and even death if it is not treated immediately. Tylenol poisoningThis is the leading cause of severe liver injury that requires liver transplantation in the United States.
There is currently one treatment available for it. It can only prevent liver damage if it is taken within a few hours of overdose.
We tested the new drug on mice that had suffered liver damage due to toxic Tylenol dosages. We found that one dose was able to decrease liver injury biomarkers – proteins the liver releases when injured – in the blood and reduce liver tissue death.
These findings suggest that liver cell regeneration and tissue repair are happening.
Reduced transplantation requirements
Improved treatments for liver diseases are one way to reduce liver transplantation shortfalls. Although current drugs can cure many of the conditions, they are not effective for liver transplantation. hepatitis COther liver diseases, such as a viral infection that causes inflammation and liver damage, have not seen the same improvements.
Many patients end up needing a transplant because there are not many effective treatments for nonalcoholic fatty liver disease or alcoholic liver disease.
My team and i believe that increasing the liver’s capacity to heal itself could prevent the need for transplantation. Research into drugs that stimulate liver regeneration could help reduce the global burden of liver disease.
Satdarshan MongaProfessor of Pathology & Medicine University of Pittsburgh Health Sciences
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