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- Title
ZNRF3 Regulates Collagen-Induced Arthritis Through NF-kB and Wnt Pathways.
- Authors
Liang, Jing Jing; Li, Hao Ran; Chen, Yong; Zhou, Zaixin; Shi, Ye Qing; Zhang, Lan Ling; Xin, Lei; Zhao, Dong Bao
- 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.
- Subjects
COLLAGEN-induced arthritis; UBIQUITIN ligases; RHEUMATOID arthritis; ZINC-finger proteins; WNT signal transduction
- Publication
Inflammation, 2020, Vol 43, Issue 3, p1077
- ISSN
0360-3997
- Publication type
Article
- DOI
10.1007/s10753-020-01193-1