Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
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.

« Previous
[1]
Ghouri A, Conaghan PG. Prospects for therapies in osteoarthritis. Calcif Tissue Int 2021; 109(3): 339-50.
[http://dx.doi.org/10.1007/s00223-020-00672-9] [PMID: 32055890]
[2]
Hunter DJ, March L, Chew M. Osteoarthritis in 2020 and beyond: A lancet commission. Lancet 2020; 396(10264): 1711-2.
[http://dx.doi.org/10.1016/S0140-6736(20)32230-3] [PMID: 33159851]
[3]
Sircana G, Passiatore M, Capasso L, Saccomanno MF, Maccauro G. Infections in arthroscopy. Eur Rev Med Pharmacol Sci 2019; 23(S2): 279-87.
[PMID: 30977895]
[4]
Jamil M, Dandachli W, Noordin S, Witt J. Hip arthroscopy: Indications, outcomes and complications. Int J Surg 2018; 54(Pt B): 341-4.
[http://dx.doi.org/10.1016/j.ijsu.2017.08.557] [PMID: 28823795]
[5]
Nha KW, Kim HS, Cho ST, Bae JH, Jang KM, Kim SG. Arthroscopy‐controlled medial reefing and lateral release for recurrent patellar dislocation: Clinical, radiologic outcomes and complications. BMC Musculoskelet Disord 2021; 22(1): 430.
[http://dx.doi.org/10.1186/s12891-021-04300-x] [PMID: 33971864]
[6]
Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: Current understanding with therapeutic implications. Arthritis Res Ther 2017; 19(1): 18.
[http://dx.doi.org/10.1186/s13075-017-1229-9] [PMID: 28148295]
[7]
Zhang L, Li M, Li X, et al. Characteristics of sensory innervation in synovium of rats within different knee osteoarthritis models and the correlation between synovial fibrosis and hyperalgesia. J Adv Res 2022; 35: 141-51.
[http://dx.doi.org/10.1016/j.jare.2021.06.007] [PMID: 35003798]
[8]
Zhang L, Xing R, Huang Z, et al. Synovial fibrosis involvement in osteoarthritis. Front Med 2021; 8: 684389.
[http://dx.doi.org/10.3389/fmed.2021.684389]
[9]
Liu S, Cao C, Zhang Y, et al. PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis. J Orthop Surg Res 2019; 14(1): 425.
[http://dx.doi.org/10.1186/s13018-019-1394-4] [PMID: 31829201]
[10]
Maglaviceanu A, Wu B, Kapoor M. Fibroblast‐like synoviocytes: Role in synovial fibrosis associated with osteoarthritis. Wound Repair Regen 2021; 29(4): 642-9.
[http://dx.doi.org/10.1111/wrr.12939] [PMID: 34021514]
[11]
Li J, Peng L, Bai W, et al. Biliverdin protects against cerebral ischemia/reperfusion injury by regulating the miR-27a-3p/Rgs1 Axis. Neuropsychiatr Dis Treat 2021; 17: 1165-81.
[http://dx.doi.org/10.2147/NDT.S300773] [PMID: 33911865]
[12]
Feng Z, Zhou J, Liu Y, et al. Epithelium- and endothelium-derived exosomes regulate the alveolar macrophages by targeting RGS1 mediated calcium signaling-dependent immune response. Cell Death Differ 2021; 28(7): 2238-56.
[http://dx.doi.org/10.1038/s41418-021-00750-x] [PMID: 33753901]
[13]
Elter E, Wagner M, Buchenauer L, Bauer M, Polte T. Phthalate exposure during the prenatal and lactational period increases the susceptibility to rheumatoid arthritis in mice. Front Immunol 2020; 11: 550.
[http://dx.doi.org/10.3389/fimmu.2020.00550]
[14]
Hu X, Tang J, Zeng G, et al. RGS1 silencing inhibits the inflammatory response and angiogenesis in rheumatoid arthritis rats through the inactivation of Toll‐like receptor signaling pathway. J Cell Physiol 2019; 234(11): 20432-42.
[http://dx.doi.org/10.1002/jcp.28645] [PMID: 31012109]
[15]
Katoh M. Multi-layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β catenin signaling activation (Review). Int J Mol Med 2018; 42(2): 713-25.
[http://dx.doi.org/10.3892/ijmm.2018.3689] [PMID: 29786110]
[16]
Ku H C, Cheng C F. Master regulator ACTIVATING TRANSCRIPTION FACTOR 3 (ATF3) in metabolic homeostasis and cancer. Front Endocrinol 2020; 11: 556.
[http://dx.doi.org/10.3389/fendo.2020.00556] [PMID: 32922364]
[17]
Hu H, Zhang F, Li L, et al. Identification and validation of ATF3 serving as a potential biomarker and correlating with pharmacotherapy response and immune infiltration characteristics in rheumatoid arthritis. Front Mol Biosci 2021; 8: 761841.
[http://dx.doi.org/10.3389/fmolb.2021.761841]
[18]
Li X, Li Y, Yang X, et al. PR11‐364P22.2/ATF3 protein interaction mediates IL‐1β‐induced catabolic effects in cartilage tissue and chondrocytes. J Cell Mol Med 2021; 25(13): 6188-202.
[http://dx.doi.org/10.1111/jcmm.16561] [PMID: 34037306]
[19]
Chan CM, Macdonald CD, Litherland GJ, et al. Cytokine-induced MMP13 expression in human chondrocytes is dependent on activating transcription factor 3 (ATF3) regulation. J Biol Chem 2017; 292(5): 1625-36.
[http://dx.doi.org/10.1074/jbc.M116.756601] [PMID: 27956552]
[20]
Qadri MM, Jay GD, Ostrom RS, Zhang LX, Elsaid KA. cAMP attenuates TGF-β’s profibrotic responses in osteoarthritic synoviocytes: Involvement of hyaluronan and PRG4. Am J Physiol Cell Physiol 2018; 315(3): C432-43.
[http://dx.doi.org/10.1152/ajpcell.00041.2018] [PMID: 29898378]
[21]
Kuo SJ, Yang WH, Liu SC, Tsai CH, Hsu HC, Tang CH. TRANSFORMING GROWTH FACTOR β1 enhances heme oxygenase 1 expression in human synovial fibroblasts by inhibiting microRNA 519b synthesis. PLoS One 2017; 12(4): e0176052.
[http://dx.doi.org/10.1371/journal.pone.0176052] [PMID: 28423042]
[22]
Feng D, Yu J, Bao L, Fan D, Zhang B. Inhibiting RGS1 attenuates secondary inflammation response and tissue degradation via the TLR/TRIF/NF-kappaB pathway in macrophage post spinal cord injury. Neurosci Lett 2022; 768: 136374.
[http://dx.doi.org/10.1016/j.neulet.2021.136374] [PMID: 34852285]
[23]
Patel J, McNeill E, Douglas G, et al. RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling. Nat Commun 2015; 6: 6614.
[http://dx.doi.org/10.1038/ncomms7614]
[24]
Wu C, Lin H, Zhang X. Inhibitory effects of pirfenidone on fibroblast to myofibroblast transition in rheumatoid arthritis-associated interstitial lung disease via the downregulation of ACTIVATING TRANSCRIPTION FACTOR 3 (ATF3). Int Immunopharmacol 2019; 74: 105700.
[http://dx.doi.org/10.1016/j.intimp.2019.105700] [PMID: 31228816]
[25]
Kim DE, Procopio MG, Ghosh S, et al. Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation. J Exp Med 2017; 214(8): 2349-68.
[http://dx.doi.org/10.1084/jem.20170724] [PMID: 28684431]
[26]
Wang XM, Liu XM, Wang Y, Chen ZY. ACTIVATING TRANSCRIPTION FACTOR 3 (ATF3) regulates cell growth, apoptosis, invasion and collagen synthesis in keloid fibroblast through TRANSFORMING GROWTH FACTOR beta (TGF-beta)/SMAD signaling pathway. Bioengineered 2021; 12(1): 117-26.
[http://dx.doi.org/10.1080/21655979.2020.1860491] [PMID: 33315500]
[27]
Li H, Yang HH, Sun ZG, Tang HB, Min JK. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019; 8(7): 290-303.
[http://dx.doi.org/10.1302/2046-3758.87.BJR-2018-0297.R1] [PMID: 31463037]
[28]
Li Z, Wang Q, Chen G, et al. Integration of gene expression profile data to screen and verify hub genes involved in osteoarthritis. Biomed Res Int 2018; 2018: 9482726.
[http://dx.doi.org/10.1155/2018/9482726]
[29]
Gao X, Sun Y, Li X. Identification of key gene modules and transcription factors for human osteoarthritis by weighted gene co-expression network analysis. Exp Ther Med 2019; 18(4): 2479-90.
[http://dx.doi.org/10.3892/etm.2019.7848] [PMID: 31572500]
[30]
Iezaki T, Ozaki K, Fukasawa K, et al. ATF3 deficiency in chondrocytes alleviates osteoarthritis development. J Pathol 2016; 239(4): 426-37.
[http://dx.doi.org/10.1002/path.4739] [PMID: 27159257]
[31]
Ferreira-Gomes J, Garcia M M, Nascimento D, et al. TLR4 antagonism reduces movement-induced nociception and atf-3 expression in experimental osteoarthritis. J Pain Re 2021; 14: 2615-27.
[http://dx.doi.org/10.2147/JPR.S317877] [PMID: 34466029]

Rights & Permissions Print Cite
Article Metrics
27
2
© 2024 Bentham Science Publishers | Privacy Policy