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ZNRF3 Regulates Collagen-Induced Arthritis Through NF-kB and Wnt Pathways

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Abstract

Although the E3 ubiquitin ligase Zinc and ring finger 3 (ZNRF3) negatively regulates the Wnt signaling pathway, its function in rheumatoid arthritis (RA) is elusive. Here, the effects and the mechanism of ZNRF3 on a mouse model of collagen-induced arthritis (CIA) and human fibroblast-like synoviocytes (FLS) obtained from RA patients were determined. Our results showed that ZNRF3 was highly expressed in tissues and FLSs compared to trauma patients. Lentivirus-mediated silencing of ZNRF3 induced apoptosis decreased cell viability and significantly attenuated inflammation in RA-FLSs via tumor necrosis-α (TNF-α). Additionally, silencing of ZNRF3 reduced knee joint damage and also decreased the level of TNF-α, IL-1β, and IL-6 in the CIA mouse model. These effects were mediated by the crosstalk between Wnt and NF-κB pathways in RA-FLS.

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Acknowledgements

The authors thank Guo Xian and all the teachers in Experimental Center, Changhai Hospital for their valuable assistance.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81671595 and 81471607).

Author information

Author notes

  1. Jing Jing Liang, Hao Ran Li and Yong Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China

    Jing Jing Liang, Hao Ran Li, Ye Qing Shi, Lan Ling Zhang, Lei Xin & Dong Bao Zhao

  2. Department of endocrinology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

    Jing Jing Liang

  3. Department of Plastic and Reconstructive Surgery, Changhai Hospital, Naval Medical University, Shanghai, China

    Yong Chen

  4. Department of Blood Transfusion, Changhai Hospital, Naval Medical University, Shanghai, China

    Zaixin Zhou

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  1. Jing Jing Liang
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Correspondence to Dong Bao Zhao.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

All procedures performed in the studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Changhai hospital+ No. CHEC2017159).

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Liang, J.J., Li, H.R., Chen, Y. et al. ZNRF3 Regulates Collagen-Induced Arthritis Through NF-kB and Wnt Pathways. Inflammation 43, 1077–1087 (2020). https://doi.org/10.1007/s10753-020-01193-1

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  • DOI: https://doi.org/10.1007/s10753-020-01193-1

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