Protein CEACAM1 Boosts Liver Transplant Success, Study Finds
A recent study conducted by researchers from the University of California, Los Angeles (UCLA), has found that a protein known as CEACAM1 plays a crucial role in enhancing the success of liver transplants. This breakthrough discovery sheds light on the molecular mechanisms underlying the protective properties of CEACAM1 and offers potential avenues for improving post-transplant outcomes.
Liver transplantation is a complex procedure that involves restoring blood flow to the organ, which can result in inflammation and tissue damage known as ischemic reperfusion injury. To tackle this challenge, the research team sought to uncover the factors that enable CEACAM1 to safeguard the liver during transplantation.
The study revealed that a protein called Hypoxia Inducible Factor 1 (HIF-1), which regulates oxygen consumption, plays a pivotal role in activating CEACAM1-S, a specific variant of CEACAM1 that mitigates cellular injury and enhances liver function in mice. Moreover, the researchers found a correlation between CEACAM1-S and HIF-1 in human donor livers, which predicted better overall transplantation outcomes and improved immune function.
Through their investigation, the team also identified an alternative gene expression pathway, known as alternative splicing, which is stimulated by oxygen stress and ischemia. This pathway enables cells to increase protein diversity during times of danger, inflammation, and injury. By manipulating this pathway, the researchers were able to induce the production of the protective CEACAM1-S variant, effectively reducing liver injury associated with transplantation.
Furthermore, in experiments conducted on animals, the researchers utilized a molecule called DMOG to stabilize HIF-1 in vivo under normal oxygen conditions. This stabilization resulted in an increase in the protective CEACAM1-S variant, providing a compelling proof-of-concept for future therapeutic studies.
The findings of this study hold significant promise for improving liver transplant outcomes and addressing organ shortage issues. The researchers suggest that CEACAM1-S may serve as a potential marker of liver quality, and efforts to boost its expression could have therapeutic benefits for both transplantation and acute liver injury.
Moving forward, the researchers plan to examine the effects of modifying gene expression using molecules called morpholinos on suboptimal human livers kept in extended cold storage. By comprehensively understanding the alternative splicing changes that occur following ischemic stress, it may be possible to rejuvenate donor organs, thereby reducing organ shortages.
Our hypothesis is that forming the ‘beneficial’ version of CEACAM1-S prior to liver transplantation has the potential to act as a checkpoint regulator of oxygen-related stress and reduce liver ischemia-reperfusion injury, notes Kenneth Dery, the lead author of the study.
In conclusion, the UCLA study underscores the significance of protein CEACAM1 in protecting the liver during transplantation. By unraveling the molecular mechanisms behind its protective properties and demonstrating strategies to enhance its effectiveness, the researchers have opened up new possibilities for improving liver transplant success rates. These findings offer hope for patients awaiting liver transplants and provide valuable insights for medical professionals working in the field.
