Researchers from the University of Illinois Urbana-Champaign, Duke University, and the Chan Zuckerberg Biohub Chicago have identified a mechanism by which excessive alcohol consumption may impair the liver’s regenerative capabilities, even after an individual ceases drinking. Their study, published in Nature Communications, reveals that alcohol-related liver damage can trap liver cells in an intermediate, non-functional state, preventing them from completing the regeneration process. This cellular limbo is driven by inflammation that disrupts RNA splicing, a critical cellular process that converts genetic instructions into functional proteins.

The investigation compared healthy liver tissue with samples from individuals suffering from alcohol-associated hepatitis or cirrhosis. In diseased livers, cells initiated the regenerative process by reverting to a progenitor-like state but failed to fully transition back to mature, functional liver cells. Instead, they remained in a quasi-progenitor state, unable to perform their normal functions. The researchers discovered that this abnormal state was associated with widespread mis-splicing of RNA across thousands of genes, largely due to deficient levels of the protein ESRP2, which is essential for proper RNA splicing. Inflammation induced by alcohol metabolism was found to suppress both the production and activity of ESRP2, leading to the mislocalization of key proteins required for regeneration. Experimental interventions that blocked specific inflammatory signals in liver cell cultures partially restored normal RNA splicing and ESRP2 levels, suggesting potential therapeutic targets to enhance liver recovery in alcohol-associated liver disease. Source

This is a summary. Read the original at sciencedaily.com.