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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

ATF3 Modulates the Proliferation, Migration, and Apoptosis of Synovial Fibroblasts after Arthroscopy by Promoting RGS1 Transcription

Author(s): Xiao He*, Lili Deng, Kang Zou, Yun Tian and Xianzhe Tang

Volume 23, Issue 9, 2023

Published on: 31 May, 2023

Page: [981 - 990] Pages: 10

DOI: 10.2174/1566524023666230417084150

Price: $65

Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease involving both cartilage and synovium. Activating transcription factor 3 (ATF3) and regulator of G protein signaling 1 (RGS1) have been reported to be up-regulated in OA. However, little is known regarding the relationship between these two genes and the mechanism of this relationship in OA development. Therefore, the present study explores the mechanism of ATF3-mediated RGS1 in the proliferation, migration, and apoptosis of synovial fibroblasts.

Methods: After the OA cell model was constructed with TGF-β1 induction, human fibroblast-like synoviocytes (HFLSs) were transfected with ATF3 shRNA or RGS1 shRNA alone or co-transfected with ATF3 shRNA and pcDNA3.1-RGS1. Then, proliferation, migration, apoptosis, and the expression of ATF3, RGS1, α-SMA, BCL-2, caspase3, and cleaved-caspase3 were measured. Meanwhile, the potential relationship between ATF3 and RGS1 was predicted and validated.

Results and Discussion: Analysis of the GSE185059 dataset suggested that RGS1 was up-regulated in OA synovial fluid exosomes. Moreover, ATF3 and RGS1 were both highly expressed in TGF-β1-induced HFLSs. Transfection of ATF3 shRNA or RGS1 shRNA significantly reduced proliferation and migration and promoted apoptosis of TGF- β1-induced HFLSs. Mechanistically, ATF3 bound to the RGS1 promoter and elevated RGS1 expression. Silencing ATF3 repressed proliferation and migration and enhanced apoptosis of TGF-β1-induced HFLSs by down-regulating RGS1.

Conclusion: ATF3 binds to the RGS1 promoter and enhances RGS1 expression to accelerate cell proliferation and block cell apoptosis in TGF-β1-induced synovial fibroblasts.

Keywords: Osteoarthritis, activating transcription factor 3, regulator of G protein signaling 1, fibroblasts, fibrosis, proliferation, migration, apoptosis.

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