Affiliation:
1. Department of Joint Surgery, Chenzhou No.1 People’s Hospital of Hunan Province, Chenzhou, 423000,
Hunan, P.R. China
2. Pediatric Intensive Care Unit, Chenzhou No.1 People’s Hospital of Hunan Province,
Chenzhou, 423000, Hunan, P.R. China
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.
Funder
Chenzhou Sports Medicine Technology Research and Development Center
Publisher
Bentham Science Publishers Ltd.
Subject
Molecular Biology,Molecular Medicine,General Medicine,Biochemistry
Cited by
2 articles.
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