PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathways

Considered as an autoimmune disease, rheumatoid arthritis (RA) is an chronic inflammatory disorder that causes inflammation of the joints. This study is performed with the aim to clarify the expression of phospholipase D1 (PLD1) in RA and its specific regulation role of RA as well as the underlying...

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Main Authors: Zhengyu Zhang, Xi Chen, Bo Gao, Guomin Sun, Yan Wang, Junke Wang, Ting Zhang, Hao Qian, Yu Zhang, Jun Huang, Rurong Sun, Jiabiao Wu, Lei Zhou
Format: Article
Language:English
Published: Taylor & Francis Group 2021-10-01
Series:Autoimmunity
Subjects:
Online Access:http://dx.doi.org/10.1080/08916934.2021.1963957
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author Zhengyu Zhang
Xi Chen
Bo Gao
Guomin Sun
Yan Wang
Junke Wang
Ting Zhang
Hao Qian
Yu Zhang
Jun Huang
Rurong Sun
Jiabiao Wu
Lei Zhou
author_facet Zhengyu Zhang
Xi Chen
Bo Gao
Guomin Sun
Yan Wang
Junke Wang
Ting Zhang
Hao Qian
Yu Zhang
Jun Huang
Rurong Sun
Jiabiao Wu
Lei Zhou
author_sort Zhengyu Zhang
collection DOAJ
description Considered as an autoimmune disease, rheumatoid arthritis (RA) is an chronic inflammatory disorder that causes inflammation of the joints. This study is performed with the aim to clarify the expression of phospholipase D1 (PLD1) in RA and its specific regulation role of RA as well as the underlying mechanisms. In this study, synovial tissue samples were collected from RA patients, and RA-fibroblast-like synoviocytes (FLSs) were subsequently isolated. The expression levels of PLD1 and pathway-related proteins were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting or immunohistochemistry (IHC). Upon shPLD1 treatment, cell viability, proliferation, migration, invasion, and the level of inflammation-related factors were measured by Cell Counting Kit-8 (CCK-8), Edu, wound healing, Transwell and enzyme-linked immunosorbent assay (ELISA). Furthermore, C-reactive protein (CRP), rheumatoid factor (RF), arthritis score and synovial tissue lesions were assessed by collecting the blood or tissues from collagen induced arthritis (CIA) model rats. Our results showed that PLD1 level was increased in RA synovial tissues. Cell viability, proliferation, migration, invasion, and the level of inflammatory factors were reduced upon PLD1 knockdown in RA-FLSs. Moreover, p-IκBα/IκBα, β-catenin, p-IKKβ/IKKβ and TCF-4 were inhibited under PLD1 knockdown treatment. PLD1 knockdown alleviated the collagen-induced addition of arthritis score, CRP and RF, as well as the filling of inflammatory cells and proliferation of synovium in CIA model rat. To sum up, knockdown of PLD1 could reduce RA-FLSs metastasis as well as inflammatory response by modulating the activity of NF-κB and Wnt/β-catenin pathways.
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spelling doaj.art-6c6e0086fbc14fde9ff23089b2e0ead82023-09-15T10:12:24ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2021-10-0154739840510.1080/08916934.2021.19639571963957PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathwaysZhengyu Zhang0Xi Chen1Bo Gao2Guomin Sun3Yan Wang4Junke Wang5Ting Zhang6Hao Qian7Yu Zhang8Jun Huang9Rurong Sun10Jiabiao Wu11Lei Zhou12Department of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Echocardiography, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Suzhou University Changzhou First People's HospitalDepartment of Rheumatology, Immunology and Hematology, Changzhou Wujin Hospital Affiliated to Jiangsu UniversityDepartment of Rheumatology and Immunology, Affiliated Changzhou No. 2 People’s Hospital with Nanjing Medical UniversityConsidered as an autoimmune disease, rheumatoid arthritis (RA) is an chronic inflammatory disorder that causes inflammation of the joints. This study is performed with the aim to clarify the expression of phospholipase D1 (PLD1) in RA and its specific regulation role of RA as well as the underlying mechanisms. In this study, synovial tissue samples were collected from RA patients, and RA-fibroblast-like synoviocytes (FLSs) were subsequently isolated. The expression levels of PLD1 and pathway-related proteins were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting or immunohistochemistry (IHC). Upon shPLD1 treatment, cell viability, proliferation, migration, invasion, and the level of inflammation-related factors were measured by Cell Counting Kit-8 (CCK-8), Edu, wound healing, Transwell and enzyme-linked immunosorbent assay (ELISA). Furthermore, C-reactive protein (CRP), rheumatoid factor (RF), arthritis score and synovial tissue lesions were assessed by collecting the blood or tissues from collagen induced arthritis (CIA) model rats. Our results showed that PLD1 level was increased in RA synovial tissues. Cell viability, proliferation, migration, invasion, and the level of inflammatory factors were reduced upon PLD1 knockdown in RA-FLSs. Moreover, p-IκBα/IκBα, β-catenin, p-IKKβ/IKKβ and TCF-4 were inhibited under PLD1 knockdown treatment. PLD1 knockdown alleviated the collagen-induced addition of arthritis score, CRP and RF, as well as the filling of inflammatory cells and proliferation of synovium in CIA model rat. To sum up, knockdown of PLD1 could reduce RA-FLSs metastasis as well as inflammatory response by modulating the activity of NF-κB and Wnt/β-catenin pathways.http://dx.doi.org/10.1080/08916934.2021.1963957fibroblast-like synoviocytes (flss)phospholipase d1 (pld1)rheumatoid arthritis (ra)collagen induced arthritis (cia)apoptosis
spellingShingle Zhengyu Zhang
Xi Chen
Bo Gao
Guomin Sun
Yan Wang
Junke Wang
Ting Zhang
Hao Qian
Yu Zhang
Jun Huang
Rurong Sun
Jiabiao Wu
Lei Zhou
PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathways
Autoimmunity
fibroblast-like synoviocytes (flss)
phospholipase d1 (pld1)
rheumatoid arthritis (ra)
collagen induced arthritis (cia)
apoptosis
title PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathways
title_full PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathways
title_fullStr PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathways
title_full_unstemmed PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathways
title_short PLD1 knockdown reduces metastasis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis by modulating NF-κB and Wnt/β-catenin pathways
title_sort pld1 knockdown reduces metastasis and inflammation of fibroblast like synoviocytes in rheumatoid arthritis by modulating nf κb and wnt β catenin pathways
topic fibroblast-like synoviocytes (flss)
phospholipase d1 (pld1)
rheumatoid arthritis (ra)
collagen induced arthritis (cia)
apoptosis
url http://dx.doi.org/10.1080/08916934.2021.1963957
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