Alcohol's Grip: Liver Cells Trapped in Limbo, Regeneration Blocked

Excessive alcohol consumption can rob the liver of its primary advantage: the capacity for self-repair. Research from the University of Illinois, Duke University, and the Chan Zuckerberg Biohub in Chicago has revealed that alcohol "locks" liver cells in an intermediate state. In this mode, they cease to function fully and cannot complete regeneration, even if an individual abstains from alcohol entirely.

Photo: Pravda.Ru by Marina Lebedeva is licensed under Free for commercial use

A mock-up of the human liver

Cells Stuck in Limbo

Under normal conditions, liver cells possess the ability to temporarily alter their specialization and divide to restore lost tissue. In cases of alcoholic hepatitis or cirrhosis, this cycle is disrupted. A comparison between healthy tissue and samples from patients with liver damage showed that cells begin the transition to a regenerative state but fail to complete it.

The consequence is cells trapped in a limbo: they no longer function as mature cells, yet they cannot reproduce. This triggers a chain reaction. The burden on the remaining healthy cells increases, prompting them to attempt to compensate. In turn, they also become "stuck" in a non-functional state, ultimately leading to liver failure.

The Role of ESRP2 Protein

RNA analysis uncovered widespread errors in the splicing of thousands of genes, attributed to a deficiency in the ESRP2 protein. This protein is crucial for ensuring the accurate assembly of proteins. When ESRP2 is scarce, proteins essential for repair are produced with errors in their "addressing" sequences. Instead of reaching the cell nucleus, where genetic control resides, they remain in the cytoplasm, rendering them useless.

Experiments conducted on mice corroborated this link. The breakdown of alcohol produces inflammatory factors that suppress the synthesis and function of ESRP2.

Therapeutic Avenues

In the laboratory, scientists successfully normalized RNA splicing and restored ESRP2 levels by blocking one of the inflammatory factor's receptors. This suggests that therapies could target the suppression of inflammatory signals, thereby enabling cells to complete their regeneration.

Furthermore, molecules from improperly spliced RNA could potentially serve as biomarkers for the early diagnosis of alcoholic liver disease.

Source: This commentary was adapted from an original Russian-language publication by Pravda.Ru.