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Wilforine inhibits rheumatoid arthritis pathology through the Wnt11/β-catenin signaling pathway axis.


ABSTRACT:

Background

Wilforine (WFR) is a monomeric compound of the anti-RA plant Tripterygium wilfordii Hook. f. (TwHF). Whether WFR has anti-RA effect, its molecular mechanism has not been elucidated.

Aim of the study

Our study aims to clarify how WFR inhibits fibroblast-like synovial cells (FLS) activation and improves RA through Wnt11 action on the Wnt11/β-catenin signaling pathway.

Methods

The therapeutic effect of WFR on collagen-induced arthritis (CIA) rats was evaluated using methods such as rat arthritis score. The inhibitory effects and signaling pathways of WFR on the proliferation and inflammatory response of CIA FLS and RA FLS were studied using ELISA, CCK-8, RT-qPCR, Western blot, and immunofluorescence methods.

Results

WFR could effectively alleviate the arthritis symptoms of CIA rats; reduce the levels of IL-6, IL-1β, and TNF-α in the peripheral blood of CIA rats; and inhibit the expression of MMP3 and fibronectin. The data showed that WFR has a significant inhibitory effect on FLS proliferation. Furthermore, WFR inhibited the activation of Wnt/β-catenin signaling pathway and decreased the expression of Wnt11, β-catenin, CCND1, GSK-3β, and c-Myc, while the effects of WFR were reversed after overexpression of Wnt11.

Conclusions

WFR improves RA by inhibiting the Wnt11/β-catenin signaling pathway, and Wnt11 is the direct target of WFR. This study provides a new molecular mechanism for WFR to improve RA and contributes to the clinical promotion of WFR.

SUBMITTER: Huang Y 

PROVIDER: S-EPMC10720104 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Wilforine inhibits rheumatoid arthritis pathology through the Wnt11/β-catenin signaling pathway axis.

Huang Yurong Y   Peng Yanhui Y   Li Hui H   Li Chen C   Wu Yajie Y   Wang Xiaomei X   Chang Jun J   Miao Chenggui C  

Arthritis research & therapy 20231214 1


<h4>Background</h4>Wilforine (WFR) is a monomeric compound of the anti-RA plant Tripterygium wilfordii Hook. f. (TwHF). Whether WFR has anti-RA effect, its molecular mechanism has not been elucidated.<h4>Aim of the study</h4>Our study aims to clarify how WFR inhibits fibroblast-like synovial cells (FLS) activation and improves RA through Wnt11 action on the Wnt11/β-catenin signaling pathway.<h4>Methods</h4>The therapeutic effect of WFR on collagen-induced arthritis (CIA) rats was evaluated using  ...[more]

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