Evidence map›Paper›PMID 36398888›Full record

ArticleRheumatology (Oxford, England)2023

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

Sara Martínez-Ramos, Carlos Rafael-Vidal, Beatriz Malvar-Fernández, Angela Rodriguez-Trillo, Douglas Veale, Ursula Fearon, Carmen Conde, Javier Conde-Aranda, Timothy R D J Radstake, Jose María Pego-Reigosa and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Sara Martínez-RamosRheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.ORCID 0000-0003-2055-8426
Carlos Rafael-VidalRheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.
Beatriz Malvar-FernándezRheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.
Angela Rodriguez-TrilloLaboratorio 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.
Douglas VealeRheumatology EULAR Centre of Excellence, St Vincent's University Hospital and University College Dublin, Dublin, Ireland.
Ursula FearonRheumatology EULAR Centre of Excellence, St Vincent's University Hospital and University College Dublin, Dublin, Ireland.
Carmen CondeLaboratorio 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.
Javier Conde-ArandaMolecular and Cellular Gastroenterology, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Timothy R D J RadstakeDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Jose María Pego-ReigosaRheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.
Kris A ReedquistDepartment of Rheumatology and Clinical Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Samuel GarcíaRheumatology & Immuno-mediated Diseases Research Group (IRIDIS), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain.ORCID 0000-0002-5902-2699
University Hospital Complex Of Vigo · ESInstituto de Investigación Sanitaria de Santiago · ESUtrecht University · NLUniversity College Dublin · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveClass 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.

methodsProtein 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.

resultsmRNA 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.

conclusionHOXA5 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.

Indexed as

Arthritis, RheumatoidSemaphorinsSynoviocytesCell ProliferationCells, CulturedFibroblastsHomeodomain ProteinsHumansHuman Umbilical Vein Endothelial CellsRNA, MessengerSynovial MembraneTranscription FactorsHomeodomain ProteinsHOXA5 protein, humanRNA, MessengerSemaphorinsTranscription Factorscell invasioncell migrationclass 3 semaphorinsEBF-1endothelial cellsfibroblast-like synoviocytesHOXA5individuals at riskRATCF-3

Identifiers

PMID36398888
PMCPMC10321103
OpenAlexW4309287713

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.