The Underlying Mechanism of Duanteng Yimu Decoction in Inhibiting Synovial Hyperplasia in Rheumatoid Arthritis

• Published in: Journal of immunology research 2023-05, Vol.2023, p.2340538-11
• Main Authors: Feng, Wei, Zhong, Xiao-Qin, Zheng, Xue-Xia, Liu, Qing-Ping, Liu, Min-Ying, Liu, Xiao-Bao, Lin, Chang-Song, Xu, Qiang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - metabolism; Cartilage; Cell adhesion & migration; Cell Proliferation; Cells, Cultured; Chinese medicine; Cholecystokinin; Collagen; Cytokines; Enzyme-linked immunosorbent assay; Fibroblasts; Fibroblasts - metabolism; Flow cytometry; Government agencies; Hyperplasia; Hyperplasia - drug therapy; Hyperplasia - metabolism; Hyperplasia - pathology; IL-1β; Immunology; Inflammation; Interleukin 18; Interleukin 6; Interleukin-18 - metabolism; Interleukin-6 - metabolism; Joint diseases; Leukocytes, Mononuclear - metabolism; Medical research; Mice; MicroRNAs; MicroRNAs - metabolism; miRNA; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; Osteoarthritis; Peripheral blood mononuclear cells; Rheumatoid arthritis; Signal transduction; Synovial Membrane - pathology; Synoviocytes - metabolism; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2023/2340538

Dysregulation of microRNAs (miRNAs) is associated with the pathogenesis of rheumatoid arthritis (RA). Our previous studies confirmed that Duanteng Yimu decoction (DTYMT) effectively inhibits RA fibroblast-like synoviocyte (FLS) proliferation. In this study, we investigated the influence of DTYMT on miR-221 in RA individuals. Hematoxylin–eosin (HE) staining was performed to assess histopathological alterations in collagen-induced arthritis (CIA) mice. The expression of miR-221-3p and TLR4 in PBMC, FLS, and cartilage was measured by RT-qPCR. In the in vitro experiments, DTYMT-containing serum was incubated with FLS-transfected miR-221 mimic or inhibitor. CCK-8 was performed to determine FLS proliferation, and the secretion of IL-1β, IL-6, IL-18, and TNF-α was quantified by ELISA assay. In addition, the regulation of miR-221 expression on FLS apoptosis was assessed using flow cytometry. Finally, western blot was employed to reflect TLR4/MyD88 protein levels. HE results showed that DTYMT effectively reduced synovial hyperplasia in the joints of CIA mice. RT-qPCR assay of FLS and cartilage of the model group showed that miR-221-3p and TLR4 significantly increased compared with those in the normal group. All outcomes were improved by DTYMT. The miR-221 mimic reversed the inhibitory effect of DTYMT-containing serum on FLS proliferation, the release of IL-1β, IL-18, IL-6, and TNF-α, and FLS apoptosis, as well as TLR4/MyD88 protein levels. The results showed that miR-221 promotes the activity of RA-FLS by activating TLR4/MyD88 signaling, and DTYMT treats RA by reducing miR-221 in CIA mice.