Presentation description

Hepatocellular Carcinoma (HCC) ranks as the third leading cause of cancer-related mortality globally. Risk factors for HCC include excess alcohol consumption and cirrhosis. Hepatic stellate cells (HSCs) play a crucial role in secreting extracellular matrix (e.g Laminin) to repair liver damage. Persistent overactivation of HSCs can lead to fibrous scarring and cirrhosis. Podocalyxin-like (podxl) is a gene expressed in HSCs, essential for their migratory ability into the liver for activation. This study aims to understand the role of podxl in HSC migration and its impact on the recovery from alcohol-induced liver injury.

Our research utilized a zebrafish model, chosen for its physiological similarities to humans. Zebrafish parents were genetically modified to have markers that visualize HSCs and podxl mutations created via CRISPR-Cas9 technology. Zebrafish larvae were subjected to ethanol treatment for one day, followed by a one-day recovery period in freshwater. Subsequently, the larvae were fixed, genotyped, deskinned, and antibody stained. Genetic information was extracted from the larvae tails, while their bodies were imaged for HSC count, liver size, and laminin deposition.

The results of our experiment showcased increased HSC count in wildtype larvae when it was treated with ethanol. Control and ethanol-treated podxl mutants have similar HSC count to each other and also the control wildtype. Control mutants have substantially longer and more frequent laminin deposition compared to control wildtype and ethanol-treated mutants. These results indicate that the presence of podxl does play a crucial role in regulating HSC behaviors during recovery from alcohol-induced liver damage. When podxl is mutated, genetic compensation preserves HSC count when compared to wildtype podxl. However, this genetic compensation greatly increases laminin deposition compared to wildtype podxl behavior. This effect on laminin deposition is seen to be reversed with ethanol exposure, potentially hindering liver recovery.