Could Inactivating One Gene Promote Liver Regeneration?

Does specific gene inactivation unlock lost regenerative ability in mammals?

Many animals have an astonishing ability to regenerate lost limbs and tissue, but humans are generally poor performers when it comes to regeneration. The liver is an exception to this and can recover around 70% of its tissue after damage, but when damaged by disease or chemical exposure this ability is slowly lost. Progressive liver injury from alcohol abuse, hepatitis C or liver disease leads to scarring, or cirrhosis which contributes to risk of liver cancer. 

“This research gives us ideas about new ways to treat liver damage or chronic liver disease. In humans, the gene ARID1A is mutated in several cancers, including liver cancer, pancreatic cancer, breast cancer, endometrial cancer, lung cancer, the list goes on. It is not mutated in every type of cancer, but in a significant number. Those mutations are found in 10 to 20 percent of all cancers, and the mutations render the gene inactive”

Loosening the controls on regeneration

When researchers studied a particular mice strain lacking the gene Arid1a they expected to observe increased incidence of liver cancer, because the gene is found mutated in many cases. To their surprise however, they discovered that mice with the knock out demonstrated increased liver regeneration, superior to normal. Liver tissue was recuperated faster, and less fibrosis occurred in response to any damage. Mice lacking this Arid1a gene also showed improved wound healing in the skin as well. 

An example of liver cirrhosis. Credit: Ed Uthman

“The livers were resistant to tissue damage and healed better, which are two good things – like playing offense and defense at the same time. These results opened up a whole new avenue of investigation for us, and through that investigation we found a new function for this gene”

A future target

No current drugs can mimic this silencing effect, but the researchers hypothesized that this gene acts as a control mechanism, and that silencing it acts as a switch unlocking inhibited regenerative pathways. The gene’s relationship with cancer needs to be explored further, but if a drug could target such a gene in humans without increasing cancer risk, then it could improve liver health in at risk patients. The research also highlights the important role certain genes play in controlling innate regenerative capacity, suggesting we may be able to coax the body one day to heal itself. 

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