New research by Fani Roumelioti in George Kollias lab reveals microRNAs Mir221/222 as key players in rheumatoid arthritis.
A new published study by Kollias lab at Fleming uncovers a critical role for microRNAs Mir221 and Mir222 in driving rheumatoid arthritis (RA) progression. RA is a chronic inflammatory disease that affects mainly the joints impairing movement and quality of life. One of the disease hallmarks is the expansion of arthritogenic synovial fibroblasts (SFs). SFs physiologically support and lubricate the joint cavity area. In joint pathologies these SFs expand and orchestrate the inflammatory and destructive response.
The study by Roumelioti et al. demonstrates that SF-specific overexpression of a family of miRNAs, Mir221/222, leads to a more aggressive development of arthritis in mouse models. In contrast, their deletion ameliorates the arthritic symptoms. Detailed mechanistic investigation revealed that Mir221/222 promote the expansion of pathogenic SFs by targeting cell cycle inhibitors (p27 and p57) and a chromatin remodelling component (Smarca1). Thus, targeting this family of microRNAs could offer new therapeutic strategies to combat RA's debilitating effects. This discovery opens the door for novel treatments addressing fibroblast-driven inflammation, with potential applications for other inflammatory diseases.
Publication: Roumelioti F, Tzaferis C, Konstantopoulos D, Papadopoulou D, Prados A, Sakkou M, Liakos A, Chouvardas P, Meletakos T, Pandis Y, Karagianni N, Denis MC, Fousteri M, Armaka M, Kollias G. Mir221/222 drive synovial hyperplasia and arthritis by targeting cell cycle inhibitors and chromatin remodeling components. Elife. 2024 Sep 5;13:e84698.
https://doi.org/10.7554/eLife.84698
