Open Access

Kirenol relieves rheumatoid arthritis by targeting the TWEAK/Fn14 pathway

  • Authors:
    • Zixin Chen
    • Jinxuan Wang
    • Lijuan Xiao
    • Zhihui Chen
    • Wenchuan Luo
    • Wen Xu
    • Ya Lin
    • Mei Huang
    • Yuqian Zhang
    • Yinghao Wang
    • Yaping Chen
    • Lihong Nan
  • View Affiliations

  • Published online on: July 14, 2025     https://doi.org/10.3892/ijmm.2025.5586
  • Article Number: 145
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fibroblast‑like synoviocytes (FLSs) are the primary drivers of synovial tissue hyperplasia in rheumatoid arthritis (RA). Activation of the tumor necrosis factor‑like weak inducer of apoptosis (TWEAK)/fibroblast growth factor‑inducible immediate‑early response protein 14 (Fn14) pathway significantly contributes to the pathogenesis of RA. Kirenol (Kir), a compound with anti‑inflammatory and antirheumatic properties, has an unclear mechanism of action. To comprehensively investigate the effects and potential mechanisms of Kir on RA, the present study employed both an in vitro model of transforming growth factor‑β1 (TGF‑β1)‑induced human fibroblast‑like MH7A synoviocytes proliferation and an in vivo collagen‑induced arthritis (CIA) rat model. The effects of Kir on synovial fibroblasts were detected via flow cytometry, ELISA, hematoxylin and eosin staining, safranin‑O/fast green staining, immunohistochemistry, immunofluorescence and western blotting. Kir ameliorated pathological damage in the synovial tissue of CIA rats, suppressed rheumatoid factor production, regulated the T helper 17 cells/regulatory T cell balance and mitigated joint inflammation and swelling. Additionally, Kir markedly downregulated the protein levels of the TWEAK/Fn14 pathway in synovial tissue. Surface plasmon resonance demonstrated that Kir could specifically bind to Fn14. Kir significantly suppressed the TGF‑β1‑mediated aberrant proliferation and migration of MH7A cells. However, the overexpression of Fn14 reversed the inhibitory effects of Kir on the abnormal proliferation and migration of cells, as did the activation of the TWEAK/Fn14 pathway. These results suggest that Kir possesses anti‑RA properties by inhibiting abnormal immune‑inflammatory responses, as well as synovial cell proliferation and migration. These effects of Kir may be linked to a decrease in the activity of the TWEAK/Fn14 pathway.
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October-2025
Volume 56 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Chen Z, Wang J, Xiao L, Chen Z, Luo W, Xu W, Lin Y, Huang M, Zhang Y, Wang Y, Wang Y, et al: Kirenol relieves rheumatoid arthritis by targeting the TWEAK/Fn14 pathway. Int J Mol Med 56: 145, 2025.
APA
Chen, Z., Wang, J., Xiao, L., Chen, Z., Luo, W., Xu, W. ... Nan, L. (2025). Kirenol relieves rheumatoid arthritis by targeting the TWEAK/Fn14 pathway. International Journal of Molecular Medicine, 56, 145. https://doi.org/10.3892/ijmm.2025.5586
MLA
Chen, Z., Wang, J., Xiao, L., Chen, Z., Luo, W., Xu, W., Lin, Y., Huang, M., Zhang, Y., Wang, Y., Chen, Y., Nan, L."Kirenol relieves rheumatoid arthritis by targeting the TWEAK/Fn14 pathway". International Journal of Molecular Medicine 56.4 (2025): 145.
Chicago
Chen, Z., Wang, J., Xiao, L., Chen, Z., Luo, W., Xu, W., Lin, Y., Huang, M., Zhang, Y., Wang, Y., Chen, Y., Nan, L."Kirenol relieves rheumatoid arthritis by targeting the TWEAK/Fn14 pathway". International Journal of Molecular Medicine 56, no. 4 (2025): 145. https://doi.org/10.3892/ijmm.2025.5586