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

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.

• Authors: Wei Zhou, Qin Shen, Hui Wang, Jie Yang, Chen Zhang, Zijing Deng, Keyan Wu, Yang Zhou, Jing Zeng, Yu Zhang, Weigan Shen
• Journal: Journal of immunology research (J Immunol Res) Vol. 2020 Pg. 9510594 ( 2020) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 33145365 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Wei Zhou et al.

Chemical References

• Adaptor Proteins, Signal Transducing
• Intracellular Signaling Peptides and Proteins
• NF-kappa B
• Transcription Factors
• Transcriptional Coactivator with PDZ-Binding Motif Proteins
• WWTR1 protein, human
• YAP-Signaling Proteins
• YAP1 protein, human

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Apoptosis
• Arthritis, Rheumatoid (metabolism)
• Autophagy
• Cell Movement
• Cells, Cultured
• Fibroblasts (physiology)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• NF-kappa B
• Signal Transduction
• Synovial Membrane (immunology)
• Synoviocytes (physiology)
• Transcription Factors (genetics, metabolism)
• Transcriptional Coactivator with PDZ-Binding Motif Proteins
• YAP-Signaling Proteins