Effects of Catalpol on the Proliferation of Rheumatoid Arthritis Fibroblast Synovial Cells and YAP/TAZ Signaling Pathway

This article explores the effects of catalpol on proliferation of FLS (fibroblast-like synoviocytes) and YAP (yes-associated protein)/TAZ (transcriptional co-activator with PDZ-binding motif) signaling pathway in RA (rheumatoid arthritis). Human arthritis fibroblast like synovial cells HFLS-RA were cultured in vitro and induced with 20 ng/mL TNF-α (tumor necrosis factor-α) to establish a RA cell model, SD rats were selected to construct an RA animal model using type II collagen, and then randomly grouped into model group, catalpol group, empty group, and catalpol+YAP overexpression group, 10 per group, another 10 SD rats and normal cultured HFLS-RA cells were selected as the control group, after grouping and treatment with catalpol, empty plasmid, and YAP overexpression plasmid, CCK-8 method and TUNEL staining, flow cytometry were applied to detect the proliferation and apoptosis of HFLS-RA cells in each group, respectively; the foot volume of rats in each group was measured by the toe measuring instrument and the arthritis score was performed according to the 5-level scoring method; TUNEL staining was applied to detect apoptosis in the synovial tissue of rats in each group; ELISA (enzyme-linked immunosorbent assay) was applied to detect the levels of pro-inflammatory factors IL-1β (interleukin-1β), MCP-1 (monocyte chemotactic protein-1), and IL-6 in serum of HFLS-RA cells and RA rats in each group; immunoblotting experiments were applied to detect the expression of proliferation and YAP/TAZ signaling related proteins in HFLS-RA cells and synovial tissue of RA rats in each group. The results showed that, compared with the control group, the survival rate of HFLS-RA cells, rat foot volume and arthritis score, the levels of IL-6, MCP-1, IL-1β in HFLS-RA cells and in serum of RA rats, and the expression of Cyclin D1, YAP and TAZ proteins in HFLS-RA cells and in synovial tissue of RA rats in the model group increased (P<0.05), while the apoptosis rate of HFLS-RA cells and the apoptosis ratio of synovial tissue cells in rat decreased (P<0.05). Compared with the model group, the survival rate of HFLS-RA cells, rat foot volume and arthritis score, the levels of IL-6, MCP-1, IL-1β in HFLS-RA cells and in serum of RA rats, and the expression of Cyclin D1, YAP and TAZ proteins in HFLSRA cells and in synovial tissue of RA rats in the catalpol group decreased (P<0.05), the apoptosis rate of HFLS-RA cells and the apoptosis ratio of synovial tissue cells in rat increased (P<0.05); there was no significant change in all indicators in the empty load group (P>0.05). Compared with the catalpol group, the survival rate of HFLS-RA cells, rat foot volume and arthritis score, the levels of IL-6, MCP-1, IL-1β in HFLS-RA cells and in serum of RA rats, and the expression of Cyclin D1, YAP and TAZ proteins in HFLS-RA cells and in synovial tissue of RA rats in the catalpol+YAP overexpression group increased (P<0.05), while the apoptosis rate of HFLS-RA cells and the apoptosis ratio of synovial tissue cells in rat decreased (P<0.05). In short, catalpol can reduce inflammation levels in RA rats and cell models by weakening YAP/TAZ signaling activity, thereby inhibiting FLS proliferation and alleviating arthritis symptoms in RA rats.

CSTR: 32200.14.cjcb.2024.06.0010