Knockdown of YAP/TAZ Inhibits the Migration and Invasion of Fibroblast Synovial Cells in Rheumatoid Arthritis by

Wei Zhou1,2, Qin Shen3, Hui Wang1

  • 1Department of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, China.

Insights

Knocking down YAP and TAZ in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) inhibits migration and invasion by promoting autophagy. This suggests YAP/TAZ and autophagy are potential therapeutic targets for RA treatment.

Area of Science:

  • Rheumatology
  • Cell Biology
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) is characterized by inflammation and joint destruction.
  • Fibroblast-like synoviocytes (FLS) play a critical role in RA pathogenesis.
  • The roles of YAP/TAZ and autophagy in RA-FLS migration and invasion are not fully understood.

Purpose of the Study:

  • To investigate the effect of yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) knockdown on RA-FLS migration and invasion.
  • To explore the relationship between YAP/TAZ and autophagy in RA-FLS.

Main Methods:

  • Stable knockdown of YAP or TAZ in RA-FLS using lentiviral vectors.
  • Wound healing and Transwell assays to assess cell migration and invasion.
  • RT-qPCR and Western blotting to analyze gene and protein expression, including autophagy markers.

Main Results:

  • YAP and TAZ are upregulated in RA-FLS.
  • Knockdown of YAP/TAZ inhibited RA-FLS migration and invasion, reduced N-cadherin and Vimentin, and increased E-cadherin and β-catenin.
  • YAP/TAZ knockdown promoted autophagy, indicated by increased LC3B-II and ULK1, and decreased SQSTM1/p62.
  • Inhibiting autophagy partially reversed the effects of YAP/TAZ knockdown on migration and invasion.

Conclusions:

  • YAP/TAZ signaling pathways are crucial for RA-FLS migration and invasion.
  • Autophagy is involved in the regulation of RA-FLS migration and invasion by YAP/TAZ.
  • Targeting YAP/TAZ and autophagy may offer novel therapeutic strategies for rheumatoid arthritis.

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