Prediction of Rheumatoid Arthritis and Finding Key Substances for Treatment
Oct 02, 2024
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A research team led by Professor Kim Rak-kyun of Yonsei University Medical School's Department of Life Sciences discovered that the 'Gelsolin (GSN)' protein inhibits the activation of a large amount of 'NLRP3 inflammatory complex' in rheumatoid arthritis patients.
Rheumatoid arthritis is constantly inflamed and damages joints. It is most important to quickly detect and manage the condition before it becomes serious because it leads to the destruction of cartilage and bones. Various diagnostic markers have been proposed so far, but the mechanism of action has not been clearly identified, so there is a limit to their clinical use. Gelsolin (GSN), which the researchers noted, is a protein involved in cell shape changes and in the inhibition of mobility and apoptosis.
It is found in low concentrations in the blood of rheumatoid arthritis patients, and the researchers have found that gelsolin inhibits the activity of NLRP3 inflammatory complexes. The NLRP3 inflammatory complex is associated with IL-1β, an inflammatory cytokine, and promotes the inflammatory response of rheumatoid arthritis.
Professor Kim Rak-kyun's research team confirmed that gelsolin not only helps predict and diagnose rheumatoid arthritis early, but can also be used to develop new treatments.
The research team used gene editing technology to induce rheumatoid arthritis and compare inflammatory responses in gelsolin-deficient mice and normal mice.
As a result, the gelsolin-deficient rat group showed arthritis symptoms with more severe swelling in the feet and ankles, and inflammatory cytokines were excessively secreted.
These results demonstrate that a lack of gelsolin overactivates the NLRP3 inflammatory complex, which exacerbates rheumatoid arthritis symptoms. This means that the decrease in gelatin observed in rheumatoid arthritis patients is not a simple phenomenon, but is closely linked to disease progression.
In addition, the researchers also found that gelatin plays a role in suppressing excessive inflammatory responses by maintaining intracellular calcium balance and mitochondrial stability. Gelsolin combined with NLRP3 to interfere with the formation of inflammatory complexes and to inhibit the migration of NLRP3 inflammatory complexes to mitochondria. As a result, the effect of reducing the inflammatory response was found.
This suggests that gelsoline can be utilized as a diagnostic marker and therapeutic target substance in various inflammatory diseases besides rheumatoid arthritis.
Professor Kim Lak-gyun confirmed that a protein called "gelsolin" is an important factor in controlling rheumatoid arthritis. This study expects to make a significant breakthrough in the prediction and treatment of rheumatoid arthritis, which has long been at its limit."
In the future, we will study new treatment strategies to control gelatin to improve the prediction and treatment efficiency of inflammatory diseases such as rheumatoid arthritis, he said.
The study was conducted as an international joint study with Nihon University of Medicine, Osaka University, and Keio University, and was published in the journal Cell Death & Differentiation' published by Nature.
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