Researchers have discovered why the liver stops regenerating when damaged by alcohol. Inflammatory processes block the maturation of liver cells and disrupt RNA splicing, reports the website infohub.kz.
Scientists from the University of Illinois at Urbana-Champaign, Duke University, and the Chan Zuckerberg Biohub Chicago have uncovered the reasons behind the liver's loss of regenerative capacity in alcoholic liver disease. The findings were published in the journal Nature Communications.
Under normal conditions, healthy liver cells, when damaged, temporarily revert to a state similar to embryonic stem cells, actively divide, and then mature again to perform their functions. However, analysis of tissue samples from patients with alcoholic hepatitis and cirrhosis showed that cells get stuck in an intermediate state. They lose the ability to function as adult cells but cannot complete the division process. As a result, the remaining healthy tissue is subjected to increased stress, triggering a cascade of similar failures and leading to liver failure.
The study authors found that the cause of this cellular 'stalling' is a disruption in RNA splicing—the process of assembling molecular instructions for protein synthesis. Due to alcohol-induced inflammation, levels of the protein ESRP2, which is responsible for proper RNA splicing, drop sharply in cells. Consequently, proteins crucial for regeneration accumulate in the cytoplasm instead of entering the nucleus.
In experiments on mice, the scientists demonstrated that blocking inflammatory signals restores normal ESRP2 levels and corrects RNA splicing. The authors hope these findings will pave the way for new diagnostic methods and therapeutic drugs to treat severe liver damage without the need for organ transplantation.