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

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 mec...

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Main Authors: Wei Zhou, Qin Shen, Hui Wang, Jie Yang, Chen Zhang, Zijing Deng, Keyan Wu, Yang Zhou, Jing Zeng, Yu Zhang, Weigan Shen
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/9510594
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author Wei Zhou
Qin Shen
Hui Wang
Jie Yang
Chen Zhang
Zijing Deng
Keyan Wu
Yang Zhou
Jing Zeng
Yu Zhang
Weigan Shen
author_facet Wei Zhou
Qin Shen
Hui Wang
Jie Yang
Chen Zhang
Zijing Deng
Keyan Wu
Yang Zhou
Jing Zeng
Yu Zhang
Weigan Shen
author_sort Wei Zhou
collection DOAJ
description 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.
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spelling doaj-art-ad165a1f7cf74b61895fe4eff1d803cd2025-02-03T06:05:28ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/95105949510594Knockdown of YAP/TAZ Inhibits the Migration and Invasion of Fibroblast Synovial Cells in Rheumatoid Arthritis by Regulating AutophagyWei Zhou0Qin Shen1Hui Wang2Jie Yang3Chen Zhang4Zijing Deng5Keyan Wu6Yang Zhou7Jing Zeng8Yu Zhang9Weigan Shen10Department of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaDepartment of Rheumatology, The Second People’s Hospital of Lianyungang, Lianyungang, ChinaDepartment of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaDepartment of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaDepartment of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaDepartment of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaDepartment of Rheumatology, Affiliated Hospital of Yangzhou University, Yangzhou, ChinaDepartment of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaDepartment of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaDepartment of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaDepartment of Cell Biology, School of Medicine of Yangzhou University, Yangzhou, ChinaThe 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.http://dx.doi.org/10.1155/2020/9510594
spellingShingle Wei Zhou
Qin Shen
Hui Wang
Jie Yang
Chen Zhang
Zijing Deng
Keyan Wu
Yang Zhou
Jing Zeng
Yu Zhang
Weigan Shen
Knockdown of YAP/TAZ Inhibits the Migration and Invasion of Fibroblast Synovial Cells in Rheumatoid Arthritis by Regulating Autophagy
Journal of Immunology Research
title Knockdown of YAP/TAZ Inhibits the Migration and Invasion of Fibroblast Synovial Cells in Rheumatoid Arthritis by Regulating Autophagy
title_full Knockdown of YAP/TAZ Inhibits the Migration and Invasion of Fibroblast Synovial Cells in Rheumatoid Arthritis by Regulating Autophagy
title_fullStr Knockdown of YAP/TAZ Inhibits the Migration and Invasion of Fibroblast Synovial Cells in Rheumatoid Arthritis by Regulating Autophagy
title_full_unstemmed Knockdown of YAP/TAZ Inhibits the Migration and Invasion of Fibroblast Synovial Cells in Rheumatoid Arthritis by Regulating Autophagy
title_short Knockdown of YAP/TAZ Inhibits the Migration and Invasion of Fibroblast Synovial Cells in Rheumatoid Arthritis by Regulating Autophagy
title_sort knockdown of yap taz inhibits the migration and invasion of fibroblast synovial cells in rheumatoid arthritis by regulating autophagy
url http://dx.doi.org/10.1155/2020/9510594
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