New scientific studies have pinpointed the protein RNF41 as a primary therapeutic focus for the management of persistent liver ailments. The study illustrates that in mouse models, augmenting the production of this protein can lessen inflammation and stimulate liver regeneration.
The recently conducted research unveils the involvement of the RNF41 protein in liver fibrosis.
The RNF41 protein has the potential to be a novel treatment focus in combating two chronic liver diseases: cirrhosis and liver inflammation, according to a research directed by investigator Pedro Melgar-Lesmes from the Department of Biomedicine at the Faculty of Medicine and Health Sciences of the University of Barcelona. The results were recently printed in the scientific journal, Science Translational Medicine.
This research could result in the creation of medicines that intensify the production of RNF41 protein in macrophages, immune system defense cells that have a crucial function in responding to liver damage and in the advancement of chronic liver disease.
“This prospective treatment focus exemplifies a novel key regulator of the part macrophages play in controlling chronic liver diseases and other diseases typified by inflammation and fibrosis,” states 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).
“Additionally, our findings underline that controlling innate immunity, especially the activity of macrophages, is crucial in battling liver fibrosis and improving liver regeneration.”
So, what part does the RNF41 protein play in liver fibrosis?
The study shows that the expression of RNF41, a protein linked with inflammatory processes, is diminished in macrophages taken from liver specimens of patients suffering from liver cirrhosis, regardless of the cause of the disease. Likewise, in mice with liver fibrosis, the protein’s expression in liver macrophages is also lessened.
The group discovered that a drawn-out inflammation process in liver macrophage cell cultures results in a decrease in the RNF41 protein. “Hence, chronic inflammation could be the cause for the diminished RNF41 in macrophages,” explains Melgar-Lesmes.
In mouse models where the function of the RNF41 protein could be reinstated, the results demonstrated enhanced removal of fibrosis, decreased liver inflammation, and amplified liver regeneration.
Ground-breaking Techniques
To achieve these outcomes, the team employed an innovative method utilizing dendrimer-graphite nanoparticles (DGNP), molecules that have beneficial traits in biomedicine. Moreover, the team also used a method to specifically isolate macrophages using magnetic spheres attached to antibodies (MACS). This showed that these nanoparticles are effective for selective gene therapy in inflamed macrophages in a fibrotic liver.
Parallelly, in vitro studies confirm that if the RNF41 protein vanishes in macrophages of fibrotic mouse livers, it instigates a surge of inflammatory cytokines that results in increased fibrosis, liver damage, and some mortality. “This confirms that the RNF41 protein is essential to overcome fibrosis and chronic inflammation in liver disease,” asserts Melgar-Lesmes.
The team’s future research plans will concentrate on discovering which proteins control the RNF41 protein in macrophages. “This will empower us to create new drugs to enhance the expression of this critical protein in the regulation of macrophages’ role in inflammation and liver fibrosis”, concludes the researcher.
Reference: “RNF41 orchestrates macrophage-driven fibrosis resolution and hepatic regeneration” 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
