3rd Edition Of Plant Science and Molecular Biology World Conference 2026

Abstract

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial tissue, wherein the pathological crosstalk between rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and macrophages is a core driver of persistent inflammation. Saussurea involucrata (SI), an effective traditional medicine for anti-RA therapy, its specific molecular mechanisms for modulating this intercellular communication remain to be elucidated. Methods: This study first evaluated the effect of SI aqueous extract on the proliferative activity of RA-FLS. Subsequently, we isolated exosomes secreted by RA-FLS with or without SI pre-treatment and co-cultured them with THP-1-derived macrophages to investigate their regulatory effects on macrophage polarization. High-throughput sequencing was employed to screen for differentially expressed miRNAs within the exosomes, and key signaling pathways were identified through bioinformatics and dual-luciferase reporter assays. Results: The SI aqueous extract effectively inhibited the abnormal proliferation of RA-FLS. Exosomes derived from RA-FLS significantly induced macrophage polarization towards a pro-inflammatory M1 phenotype, whereas this pro-inflammatory effect was markedly attenuated following SI pre-treatment. Mechanistically, we found that RA-FLS exosomes were enriched with Let-7 family miRNAs, and SI intervention effectively downregulated their expression levels. It was further confirmed that the Let-7 family negatively regulated the protein expression of retinol dehydrogenase 10 (RDH10)—a key enzyme that catalyzes the synthesis of the endogenous anti-inflammatory mediator retinoic acid—by directly targeting its mRNA 3'-UTR. Conclusion: This study unveils a novel mechanism whereby SI aqueous extract suppresses the M1 pro-inflammatory polarization of macrophages by inhibiting the secretion of Let-7-enriched exosomes from RA-FLS, which in turn relieves the suppression of RDH10 expression and restores the local anti-inflammatory action of retinoic acid. This finding not only deepens the understanding of the therapeutic mechanism of SI in RA but also provides a new scientific basis for therapeutic strategies targeting exosome-mediated communication.

Key words: Rheumatoid Arthritis; Saussurea involucrata; Exosomes; Macrophage Polarization; Let-7