2023-07-31 14:45:19
The RNF41 protein could be a new therapeutic target in the fight against two chronic liver diseases: cirrhosis and liver inflammation. This is according to a new study.
The research is the work of the team led by Alazne Moreno-Lanceta and Pedro Melgar-Lesmes, from the University of Barcelona (UB).
What was discovered in the new study could prompt the design of drugs that enhance the production of the RNF41 protein in macrophages, defensive cells of the immune system that play an essential role in the response to liver damage and in the progression of chronic liver diseases. .
“This potential therapeutic target represents a new main regulator of the role of macrophages in the control of chronic liver diseases and other diseases characterized by inflammation and fibrosis,” says expert Pedro Melgar-Lesmes, also a member of the August Pi Biomedical Research Institute. i Sunyer (IDIBAPS), the CIBER for Liver and Digestive Diseases (CIBEREHD) in Spain and the Massachusetts Institute of Technology (MIT, in the United States).
“Our discovery -he continues- highlights that the regulation of innate immunity, and specifically the activity of macrophages, is essential to fight liver fibrosis and enhance liver regeneration.”
Section of liver damaged by cirrhosis. (Photo: Dr. Edwin P. Ewing, Jr./CDC)
What is the role of the RNF41 protein in liver fibrosis?
The study reveals that the expression of RNF41 —a protein related to inflammatory processes— is lower in macrophages isolated from liver samples of patients affected by liver cirrhosis, regardless of the origin of the disease. In mice with liver fibrosis, protein expression in liver macrophages is also reduced.
The team has verified that a prolonged inflammation process in liver macrophage cell cultures causes a decrease in the RNF41 protein. “Therefore, chronic inflammation could be responsible for the reduction of RNF41 in macrophages,” points out Melgar-Lesmes.
In mice in which the function of the RNF41 protein could be restored, the results have shown that the elimination of fibrosis, the reduction of liver inflammation and the increase of liver regeneration are enhanced.
An innovative methodology
To achieve these results, an innovative methodology has been used based on the use of dendrimer-graphite nanoparticles (NDG) —molecules with functional characteristics of interest in biomedicine— designed by the team. In addition, the technique of specific isolation of macrophages has also been applied, using magnetic beads attached to antibodies (MACS). Thus, it has been shown that these nanoparticles are effective in selective gene therapy in inflamed macrophages of the fibrotic liver.
In parallel, in vitro studies confirm that if the RNF41 protein is lost in the macrophages of fibrotic mouse livers, a storm of inflammatory cytokines is triggered, leading to increased fibrosis, liver damage, and some mortality. “This tells us that the RNF41 protein is necessary to overcome fibrosis and chronic inflammation in liver disease,” says Melgar-Lesmes.
The team’s future lines of research will focus on identifying the proteins that control the RNF41 protein in macrophages. “This will allow us to design new drugs that increase the expression of this key protein in regulating the role of the macrophage in liver inflammation and fibrosis,” concludes the researcher.
The study is titled “RNF41 orchestrates macrophage-driven fibrosis resolution and hepatic regeneration”. And it has been published in the academic journal Science Translational Medicine. (Source: UB)
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