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A Cryo-pulverization Protocol for Processing Mouse Paws to Evaluate Molecular Pathways of Tissue Inflammation in a Collagen Induced Arthritis Model
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ZNRF3 Regulates Collagen-Induced Arthritis Through NF-kB and Wnt Pathways

Jing Jing Liang1,2, Hao Ran Li1, Yong Chen3

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

Inflammation
|March 4, 2020
PubMed

Insights

Zinc and ring finger 3 (ZNRF3) is highly expressed in rheumatoid arthritis (RA). Silencing ZNRF3 reduced inflammation and joint damage in RA models by impacting Wnt and NF-κB pathways.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
  • The Wnt signaling pathway plays a role in RA pathogenesis.
  • The function of E3 ubiquitin ligase Zinc and ring finger 3 (ZNRF3) in RA is not well understood.

Purpose of the Study:

  • To investigate the role and mechanism of ZNRF3 in rheumatoid arthritis.
  • To determine the effect of ZNRF3 on collagen-induced arthritis (CIA) in mice and human fibroblast-like synoviocytes (FLS) from RA patients.

Main Methods:

  • ZNRF3 expression was analyzed in RA tissues and FLS.
  • Lentivirus-mediated silencing of ZNRF3 was performed in RA-FLS and a CIA mouse model.
  • Cell viability, apoptosis, and inflammatory cytokine levels (TNF-α, IL-1β, IL-6) were measured.
  • The interplay between Wnt and NF-κB pathways was investigated.

Main Results:

  • ZNRF3 was significantly upregulated in RA tissues and FLS compared to controls.
  • Silencing ZNRF3 induced apoptosis and decreased viability in RA-FLS.
  • ZNRF3 inhibition attenuated inflammation in RA-FLS, reducing TNF-α levels.
  • In the CIA mouse model, ZNRF3 silencing reduced joint damage and inflammatory cytokine levels (TNF-α, IL-1β, IL-6).

Conclusions:

  • ZNRF3 is upregulated in rheumatoid arthritis and contributes to disease pathogenesis.
  • Targeting ZNRF3 may represent a therapeutic strategy for RA.
  • The effects of ZNRF3 modulation involve crosstalk between the Wnt and NF-κB signaling pathways.
Keywords:
NF-κB pathwayWnt/β-catenin pathwayZNRF3collagen-induced arthritisrheumatoid arthritissynovial fibroblasts

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