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Updated: Dec 2, 2025

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
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.
Abstract:
The purpose of this study was to investigate the effect of knockdown of the yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) on the migration and invasion of the rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and to preliminarily elucidate the mechanisms between YAP/TAZ and autophagy in the migration and invasion of RA-FLS. RA-FLS stable knockdown of YAP or TAZ was successfully established by using lentiviral-mediated gene knockdown techniques. Wound healing assay and Transwell assay were used to evaluate the effect of knockdown of YAP or TAZ on the migration and invasion of RA-FLS. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting assays were performed to examine the expression of indicated genes. The results showed that YAP and TAZ were upregulated in RA-FLS, and knockdown of YAP or TAZ inhibited the migration and invasion, reduced the expression of N-cadherin and Vimentin, and increased the accumulation of E-cadherin and β-catenin in RA-FLS. Our results also demonstrated that knockdown of YAP or TAZ promoted autophagy which increased the accumulation of LC3B-II and ULK1 and decreased the amount of SQSTM1/p62 in RA-FLS. Furthermore, our data displayed that inhibition of autophagy either with 3-MA or CQ can partially reverse the decrease of migration and invasion induced by YAP and TAZ knockdown in RA-FLS. Our experiments preliminarily revealed that YAP/TAZ and autophagy play important roles in the migration and invasion of RA-FLS, which might provide novel targets for the treatment of RA.
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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