HOXA5 is a key regulator of class 3 semaphorins expression in the synovium of rheumatoid arthritis patients.
Humans
Semaphorins
/ genetics
Cells, Cultured
Synovial Membrane
/ metabolism
Arthritis, Rheumatoid
/ drug therapy
Synoviocytes
/ metabolism
Human Umbilical Vein Endothelial Cells
/ metabolism
Transcription Factors
/ metabolism
RNA, Messenger
/ metabolism
Fibroblasts
/ metabolism
Cell Proliferation
Homeodomain Proteins
/ metabolism
EBF-1
HOXA5
RA
TCF-3
cell invasion
cell migration
class 3 semaphorins
endothelial cells
fibroblast-like synoviocytes
individuals at risk
Journal
Rheumatology (Oxford, England)
ISSN: 1462-0332
Titre abrégé: Rheumatology (Oxford)
Pays: England
ID NLM: 100883501
Informations de publication
Date de publication:
05 07 2023
05 07 2023
Historique:
received:
30
05
2022
accepted:
08
11
2022
medline:
7
7
2023
pubmed:
19
11
2022
entrez:
18
11
2022
Statut:
ppublish
Résumé
Class 3 semaphorins are reduced in the synovial tissue of RA patients and these proteins are involved in the pathogenesis of the disease. The aim of this study was to identify the transcription factors involved in the expression of class 3 semaphorins in the synovium of RA patients. Protein and mRNA expression in synovial tissue from RA and individuals at risk (IAR) patients, human umbilical vein endothelial cells (HUVEC) and RA fibroblast-like synoviocytes (FLS) was determined by ELISA, immunoblotting and quantitative PCR. TCF-3, EBF-1 and HOXA5 expression was knocked down using siRNA. Cell viability, migration and invasion were determined using MTT, calcein, wound closure and invasion assays, respectively. mRNA expression of all class 3 semaphorins was significantly lower in the synovium of RA compared with IAR patients. In silico analysis suggested TCF-3, EBF-1 and HOXA5 as transcription factors involved in the expression of these semaphorins. TCF-3, EBF-1 and HOXA5 silencing significantly reduced the expression of several class 3 semaphorin members in FLS and HUVEC. Importantly, HOXA5 expression was significantly reduced in the synovium of RA compared with IAR patients and was negatively correlated with clinical disease parameters. Additionally, TNF-α down-regulated the HOXA5 expression in FLS and HUVEC. Finally, HOXA5 silencing enhanced the migratory and invasive capacities of FLS and the viability of HUVEC. HOXA5 expression is reduced during the progression of RA and could be a novel therapeutic strategy for modulating the hyperplasia of the synovium, through the regulation of class 3 semaphorins expression.
Identifiants
pubmed: 36398888
pii: 6833128
doi: 10.1093/rheumatology/keac654
pmc: PMC10321103
doi:
Substances chimiques
Semaphorins
0
Transcription Factors
0
RNA, Messenger
0
HOXA5 protein, human
0
Homeodomain Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2621-2630Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.
Références
Nat Rev Rheumatol. 2016 Jan;12(1):63-8
pubmed: 26656659
Ann Rheum Dis. 2010 Jul;69(7):1389-95
pubmed: 20439288
Nat Rev Rheumatol. 2018 Jan;14(1):19-31
pubmed: 29213125
Oncol Lett. 2017 Nov;14(5):5913-5917
pubmed: 29113226
J Clin Invest. 2020 Jun 1;130(6):3005-3020
pubmed: 32364535
FASEB J. 2017 Oct;31(10):4492-4502
pubmed: 28646017
J Exp Med. 2016 Jun 27;213(7):1201-21
pubmed: 27261530
Acta Neuropsychiatr. 2012 Feb;24(1):16-25
pubmed: 25288455
Oncogene. 2008 Sep 18;27(42):5578-89
pubmed: 18504433
J Clin Invest. 2010 Aug;120(8):2684-98
pubmed: 20664171
J Exp Med. 2012 Apr 9;209(4):775-92
pubmed: 22473956
Arthritis Res Ther. 2014 Apr 01;16(2):R84
pubmed: 24690414
RMD Open. 2021 Sep;7(3):
pubmed: 34531306
Oncogene. 2016 Oct 20;35(42):5539-5551
pubmed: 27157614
Nat Rev Immunol. 2007 Jun;7(6):429-42
pubmed: 17525752
Oncotarget. 2017 Aug 3;8(39):66270-66280
pubmed: 29029510
Nature. 2000 Jun 22;405(6789):974-8
pubmed: 10879542
N Engl J Med. 2021 Aug 12;385(7):628-639
pubmed: 34379924
Arthritis Rheumatol. 2022 Jun;74(6):972-983
pubmed: 35001548
Oncol Rep. 2018 Sep;40(3):1317-1329
pubmed: 30015922
Diabetes Res Clin Pract. 2022 Feb;184:109121
pubmed: 34742786
Cancer Cell. 2015 Dec 14;28(6):815-829
pubmed: 26678341
Int J Rheum Dis. 2016 Nov;19(11):1132-1142
pubmed: 26354025
G3 (Bethesda). 2012 Sep;2(9):987-1002
pubmed: 22973536
Nat Rev Dis Primers. 2018 Feb 08;4:18001
pubmed: 29417936
Front Oncol. 2020 Jun 26;10:1035
pubmed: 32676457
Front Immunol. 2020 Mar 05;11:346
pubmed: 32210960
J Immunol. 2010 Nov 15;185(10):6373-83
pubmed: 20937848
Nat Commun. 2017 Mar 23;8:14852
pubmed: 28332497
EMBO Mol Med. 2015 Jul 20;7(10):1267-84
pubmed: 26194913
Nat Commun. 2018 May 15;9(1):1921
pubmed: 29765031
Rheumatology (Oxford). 2018 May 1;57(5):909-920
pubmed: 29471421
J Pathol. 2019 Sep;249(1):90-101
pubmed: 31020999
J Immunol. 2014 Jul 15;193(2):860-70
pubmed: 24935926
Oncogene. 2017 Oct 5;36(40):5567-5575
pubmed: 28581515
EMBO Mol Med. 2018 Feb;10(2):219-238
pubmed: 29348142
BMC Musculoskelet Disord. 2013 Jan 23;14:40
pubmed: 23343469
Cell Death Differ. 2021 Dec;28(12):3316-3328
pubmed: 34175897
Int J Mol Sci. 2019 Nov 12;20(22):
pubmed: 31726800
Int J Mol Sci. 2019 Jan 16;20(2):
pubmed: 30654587
JAMA. 2018 Oct 02;320(13):1360-1372
pubmed: 30285183
Cancer Cell. 2013 Nov 11;24(5):673-85
pubmed: 24139859
FASEB J. 2006 Oct;20(12):2150-2
pubmed: 16940438
Oncotarget. 2016 Dec 27;7(52):87431-87448
pubmed: 27911862
Neoplasia. 2002 Jan-Feb;4(1):82-7
pubmed: 11922394
Sci Rep. 2017 Sep 13;7(1):11501
pubmed: 28904399
Ann Rheum Dis. 2010 Sep;69(9):1580-8
pubmed: 20699241
Arthritis Rheum. 2010 Sep;62(9):2569-81
pubmed: 20872595
Expert Opin Ther Targets. 2012 Sep;16(9):933-44
pubmed: 22834859
J Cancer. 2017 Apr 9;8(6):1071-1081
pubmed: 28529621