” Our findings– he includes– emphasize that the regulation of innate immunity, and in particular macrophage activity, is vital to combat liver fibrosis and improve liver regeneration.”
What is the function of the RNF41 protein in liver fibrosis?
The research study reveals that the expression of RNF41– a protein associated with inflammatory procedures– is lower in macrophages isolated from liver samples of patients with liver cirrhosis, despite the origin of the disease. In mice with liver fibrosis, the expression of the protein in liver macrophages is likewise minimized.
The group has actually found that a prolonged swelling procedure in liver macrophage cell cultures leads to a decrease in RNF41 protein. “Therefore, persistent inflammation could be accountable for the decrease of RNF41 in macrophages,” says Melgar-Lesmes.
In mice in which RNF41 protein function could be restored, outcomes have shown enhanced removal of fibrosis, decreased liver inflammation, and increased liver regeneration.
An ingenious methodology
To get these outcomes, an innovative approach based upon using dendrimer-graphite nanoparticles (DGNP)– molecules with practical attributes of interest in biomedicine– created by the group has been used. In addition, the technique of specific isolation of macrophages, utilizing magnetic spheres bound to antibodies (MACS), has actually likewise been used. This has actually shown that these nanoparticles are reliable in selective gene treatment in swollen macrophages in fibrotic liver.
In parallel, in vitro studies confirm that if the RNF41 protein vanishes in macrophages of fibrotic mouse livers, it sets off a storm of inflammatory cytokines that leads to increased fibrosis, liver damage, and some death. “This tells us that RNF41 protein is needed to get rid of fibrosis and chronic inflammation in liver disease,” says Melgar-Lesmes.
The groups future lines of research study will focus on identifying which proteins control the RNF41 protein in macrophages. “This will permit us to develop brand-new drugs to increase the expression of this key protein in the policy of the function of macrophages in swelling and liver fibrosis”, concludes the researcher.
Reference: “RNF41 orchestrates macrophage-driven fibrosis resolution and hepatic regrowth” by Alazne Moreno-Lanceta, Mireia Medrano-Bosch, Yilliam Fundora, Meritxell Perramón, Jessica Aspas, Marina Parra-Robert, Sheila Baena, Constantino Fondevila, Elazer R. Edelman, Wladimiro Jiménez and Pedro Melgar-Lesmes, 12 July 2023, Science Translational Medicine. DOI: 10.1126 / scitranslmed. abq6225.
To get these results, an innovative approach based on the usage of dendrimer-graphite nanoparticles (DGNP)– molecules with practical characteristics of interest in biomedicine– developed by the group has been used. In addition, the strategy of specific seclusion of macrophages, using magnetic spheres bound to antibodies (MACS), has actually also been applied. This has demonstrated that these nanoparticles are effective in selective gene therapy in inflamed macrophages in fibrotic liver.
Reference: “RNF41 orchestrates macrophage-driven fibrosis resolution and hepatic regrowth” by Alazne Moreno-Lanceta, Mireia Medrano-Bosch, Yilliam Fundora, Meritxell Perramón, Jessica Aspas, Marina Parra-Robert, Sheila Baena, Constantino Fondevila, Elazer R. Edelman, Wladimiro Jiménez and Pedro Melgar-Lesmes, 12 July 2023, Science Translational Medicine.
New research study has actually determined the RNF41 protein as an essential target for treating chronic liver diseases, demonstrating in mice that enhancing its production can reduce swelling and boost liver regeneration.
New research study reveals the role of the RNF41 protein in liver fibrosis.
The RNF41 protein might be a new restorative target in the battle versus 2 persistent liver diseases: cirrhosis and liver swelling according to a study led by scientist Pedro Melgar-Lesmes of the Department of Biomedicine at the Faculty of Medicine and Health Sciences of the University of Barcelona. The findings were just recently released in the journal Science Translational Medicine.
This study might cause the design of drugs that enhance the production of RNF41 protein in macrophages, protective cells of the immune system that play a necessary role in the action to liver damage and in the development of chronic liver disease.
” This possible restorative target represents a new master regulator of the function of macrophages in the control of persistent liver illness and other diseases identified by swelling and fibrosis,” says Pedro Melgar-Lesmes, member of the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), the Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD) and the Massachusetts Institute of Technology (MIT, United States).