Chronic liver disease, particularly cirrhosis, may benefit from a newly discovered method that targets an inflammatory switch in the liver. Researchers at Universidad Miguel Hernández in Spain have identified the role of Platelet-Activating Factor (PAF) and its receptor (PAF-R) in exacerbating liver damage. Their findings suggest that blocking this pathway could mitigate liver injury and improve blood vessel function.
In chronic liver disease, an overactive immune response leads to persistent inflammation and scarring. The immune cells, particularly liver macrophages, become hyperactive, releasing harmful molecules that worsen the condition. These macrophages produce high levels of PAF, which not only drives inflammation but also raises portal vein pressure, contributing to further complications. Current treatments for liver disease focus primarily on managing symptoms rather than addressing underlying causes, highlighting a critical need for innovative research.
The study, led by Rubén Francés Guarinos, aimed to explore the potential of targeting PAF in patient populations and experimental models. The researchers evaluated the effects of inhibiting the PAF-R in both patients with cirrhosis and mice with chemically induced cirrhosis. Some mice received a drug that blocks PAF-R, while others were treated with a DNA methylation inhibitor prior to surgical intervention.
Through their rigorous investigation, the team assessed how gene regulation impacts the inflammatory response in liver immune cells. They analyzed the activity of Kupffer cells, which are vital to liver immune function, by exposing them to PAF and measuring the inflammatory molecules produced. The results indicated that a change in gene regulation in cirrhosis led to the overactivity of the PAF-R gene, resulting in the excessive production of PAF-R receptors. This overproduction intensifies inflammation and further damages the liver.
The researchers discovered that administering the drug BN-52021 successfully reduced liver injury and improved blood vessel function in treated mice. Notably, this treatment restored balance to the immune and inflammatory responses within the liver. “These findings suggest that drugs capable of blocking PAF action, such as BN-52021, could represent a new therapeutic line for liver cirrhosis,” stated researcher Enrique Ángel Gomis.
This research opens up new avenues for future treatments that could focus on correcting the underlying molecular switches that make the liver susceptible to damage. The overactivity of the PAF-R gene in cirrhosis is linked to epigenetic changes, which suggests that therapies aimed at restoring normal gene regulation could prevent the excessive production of PAF-R. By targeting the root of the problem, researchers could potentially calm the liver’s immune response, reducing scarring and protecting vascular function.
Rather than merely addressing the symptoms of cirrhosis, these epigenetic-based therapies could fundamentally reprogram the liver’s immune response. This approach offers a more precise and durable method for controlling inflammation and limiting disease progression. The findings of this study were published in the journal Biomedicine & Pharmacotherapy.
The urgency for effective treatments for chronic liver disease remains critical, as current options are limited and primarily focus on managing complications. As research continues to advance, the prospect of targeting the inflammatory pathways in liver disease could pave the way for innovative therapies that improve patient outcomes.
