HOXA5 is a key regulator of class 3 semaphorins expression in the synovium of rheumatoid arthritis patients.

Autor:	Martínez-Ramos S; Rheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.; Rheumatology Department, University Hospital Complex of Vigo, Vigo, Spain., Rafael-Vidal C; Rheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.; Rheumatology Department, University Hospital Complex of Vigo, Vigo, Spain., Malvar-Fernández B; Rheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.; Rheumatology Department, University Hospital Complex of Vigo, Vigo, Spain., Rodriguez-Trillo A; Laboratorio de Reumatología Experimental y Observacional, Servicio de Reumatología, Instituto de Investigación Sanitaria de Santiago (IDIS), Hospital Clínico, Universitario de Santiago de Compostela (CHUS), Servizo Galego de Saude (SERGAS), Santiago de Compostela, Spain., Veale D; Rheumatology EULAR Centre of Excellence, St Vincent's University Hospital and University College Dublin, Dublin, Ireland., Fearon U; Rheumatology EULAR Centre of Excellence, St Vincent's University Hospital and University College Dublin, Dublin, Ireland.; Department of Molecular Rheumatology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland., Conde C; Laboratorio de Reumatología Experimental y Observacional, Servicio de Reumatología, Instituto de Investigación Sanitaria de Santiago (IDIS), Hospital Clínico, Universitario de Santiago de Compostela (CHUS), Servizo Galego de Saude (SERGAS), Santiago de Compostela, Spain., Conde-Aranda J; Molecular and Cellular Gastroenterology, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain., Radstake TRDJ; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands., Pego-Reigosa JM; Rheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.; Rheumatology Department, University Hospital Complex of Vigo, Vigo, Spain., Reedquist KA; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands., García S; Rheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.; Rheumatology Department, University Hospital Complex of Vigo, Vigo, Spain.; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2023 Jul 05; Vol. 62 (7), pp. 2621-2630.
DOI:	10.1093/rheumatology/keac654
Abstrakt:	Objective: 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. Methods: 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. Results: 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. Conclusion: 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. (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu