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Article

Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction

  • Authors:
    • Yuwen Zhang
    • Xuezhi Yang
    • Chenchen Han
    • Dandan Wang
    • Yang Ma
    • Wei Wei
  • View Affiliations / Copyright

    Affiliations: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti‑inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti‑inflammatory and Immune Medicine, Hefei, Anhui 230032, P.R. China, Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti‑inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti‑inflammatory and Immune Medicine, Hefei, Anhui 230032, P.R. China
  • Article Number: 523
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    Published online on: June 17, 2022
       https://doi.org/10.3892/etm.2022.11450
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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Enhanced G protein coupled receptor kinase 2 (GRK2) translocation and prostaglandin E4 receptor (EP4) desensitization play a critical role in fibroblast‑like synoviocytes (FLS) dysfunction. Paeoniflorin‑6'O‑benzene sulfonate (CP‑25) exerts a protective effect in arthritis in the RA animal models. To demonstrate the role of Gβγ in EP4 desensitization and the mechanisms of CP‑25 that protects FLS in RA, RA‑FLS and adjuvant‑induced arthritis (AA‑FLS) were isolated from synovium of RA patients and AA rats. RA‑FLS, AA‑FLS and MH7A were treated with CP‑25, Gβγ agonist and antagonist. The cell membrane expression of EP4, GRK2, and Gβγ were detected using western blot analysis. Co‑immunoprecipitation (Co‑IP) and immunofluorescence were adopted to detect the interactions of GRK2‑Gβγ, GRK2‑EP4, and EP4‑Gβγ. Cell Counting Kit‑8 and Transwell assay were used to analyze the proliferation and migration of the FLS. An increased membrane expression of GRK2 and Gβγ, enhanced GRK2‑Gβγ interaction and decreased EP4 membrane expression in the RA synovial tissue were identified. In vitro, prostaglandin E2 (PGE2) enhanced the proliferation and migration of FLS. CP‑25 exhibited an inhibition effect similar to Gβγ inhibitor, which downregulated GRK2‑EP4 interaction, blocked the translocation of GRK2, and reversed EP4 desensitization, leading to the suppression of the proliferation and migration induced by PGE2. These results elucidated that an enhanced GRK2‑Gβγ interaction was involved in the EP4 desensitization and dysfunction. CP‑25 regulated EP4‑GRK2‑Gβγ signaling and re‑sensitized EP4 by inhibiting GRK2‑Gβγ interaction. The regulation of EP4‑Gβγ‑GRK2 signaling may be a novel potential therapeutic target in RA.
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Spandidos Publications style
Zhang Y, Yang X, Han C, Wang D, Ma Y and Wei W: Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction. Exp Ther Med 24: 523, 2022.
APA
Zhang, Y., Yang, X., Han, C., Wang, D., Ma, Y., & Wei, W. (2022). Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction. Experimental and Therapeutic Medicine, 24, 523. https://doi.org/10.3892/etm.2022.11450
MLA
Zhang, Y., Yang, X., Han, C., Wang, D., Ma, Y., Wei, W."Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction". Experimental and Therapeutic Medicine 24.2 (2022): 523.
Chicago
Zhang, Y., Yang, X., Han, C., Wang, D., Ma, Y., Wei, W."Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction". Experimental and Therapeutic Medicine 24, no. 2 (2022): 523. https://doi.org/10.3892/etm.2022.11450
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Yang X, Han C, Wang D, Ma Y and Wei W: Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction. Exp Ther Med 24: 523, 2022.
APA
Zhang, Y., Yang, X., Han, C., Wang, D., Ma, Y., & Wei, W. (2022). Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction. Experimental and Therapeutic Medicine, 24, 523. https://doi.org/10.3892/etm.2022.11450
MLA
Zhang, Y., Yang, X., Han, C., Wang, D., Ma, Y., Wei, W."Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction". Experimental and Therapeutic Medicine 24.2 (2022): 523.
Chicago
Zhang, Y., Yang, X., Han, C., Wang, D., Ma, Y., Wei, W."Paeoniflorin‑6'O‑benzene sulfonate suppresses fibroblast‑like synoviocytes proliferation and migration in rheumatoid arthritis through regulating GRK2‑Gβγ interaction". Experimental and Therapeutic Medicine 24, no. 2 (2022): 523. https://doi.org/10.3892/etm.2022.11450
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