High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis

Abstract Individuals carrying anti-citrullinated protein antibodies (ACPA) are considered at high risk of developing rheumatoid arthritis (RA). The altered expression of miRNAs contributes to the pathogenesis of RA. We aimed to identify differentially expressed miRNAs in the peripheral blood of ACPA...

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Autores principales:	Klára Prajzlerová, Olga Kryštůfková, Petra Hánová, Veronika Horváthová, Monika Gregová, Karel Pavelka, Jiří Vencovský, Ladislav Šenolt, Mária Filková
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/34a12d51cbab4668bad29802f3f1eafb
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spelling	oai:doaj.org-article:34a12d51cbab4668bad29802f3f1eafb2021-12-02T15:53:46ZHigh miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis10.1038/s41598-021-84004-32045-2322https://doaj.org/article/34a12d51cbab4668bad29802f3f1eafb2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84004-3https://doaj.org/toc/2045-2322Abstract Individuals carrying anti-citrullinated protein antibodies (ACPA) are considered at high risk of developing rheumatoid arthritis (RA). The altered expression of miRNAs contributes to the pathogenesis of RA. We aimed to identify differentially expressed miRNAs in the peripheral blood of ACPA-positive individuals with arthralgia at risk of RA compared to healthy controls (HC) and to determine their implications in the preclinical phase of RA. A comprehensive analysis of miRNAs revealed the dysregulation of miR-451 in peripheral blood mononuclear cells (PBMC) and plasma from RA-risk individuals. Higher miR-451 expression in PBMC from RA-risk individuals was further validated. Notably, miR-451 was previously shown to regulate CXCL16, a protein involved in RA pathogenesis. The expression of miR-451 in PBMC positively correlated with the CXCL16 mRNA, which could be secondary to the inflammation-induced expression of miR-451. Transfection of monocytes with pre-miR-451 in vitro resulted in the downregulation of CXCL16. Moreover, flow cytometry revealed a lower count of CXCL16-positive monocytes in RA-risk individuals. We propose that the constitutive or inflammation-induced upregulation of miR-451 in PBMC downregulates the expression of CXCL16, reduces the inflammatory milieu and thereby strives to delay the shift from the preclinical phase to the clinical manifestation of RA. This hypothesis warrants further investigation.Klára PrajzlerováOlga KryštůfkováPetra HánováVeronika HorváthováMonika GregováKarel PavelkaJiří VencovskýLadislav ŠenoltMária FilkováNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Klára Prajzlerová Olga Kryštůfková Petra Hánová Veronika Horváthová Monika Gregová Karel Pavelka Jiří Vencovský Ladislav Šenolt Mária Filková High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis
description	Abstract Individuals carrying anti-citrullinated protein antibodies (ACPA) are considered at high risk of developing rheumatoid arthritis (RA). The altered expression of miRNAs contributes to the pathogenesis of RA. We aimed to identify differentially expressed miRNAs in the peripheral blood of ACPA-positive individuals with arthralgia at risk of RA compared to healthy controls (HC) and to determine their implications in the preclinical phase of RA. A comprehensive analysis of miRNAs revealed the dysregulation of miR-451 in peripheral blood mononuclear cells (PBMC) and plasma from RA-risk individuals. Higher miR-451 expression in PBMC from RA-risk individuals was further validated. Notably, miR-451 was previously shown to regulate CXCL16, a protein involved in RA pathogenesis. The expression of miR-451 in PBMC positively correlated with the CXCL16 mRNA, which could be secondary to the inflammation-induced expression of miR-451. Transfection of monocytes with pre-miR-451 in vitro resulted in the downregulation of CXCL16. Moreover, flow cytometry revealed a lower count of CXCL16-positive monocytes in RA-risk individuals. We propose that the constitutive or inflammation-induced upregulation of miR-451 in PBMC downregulates the expression of CXCL16, reduces the inflammatory milieu and thereby strives to delay the shift from the preclinical phase to the clinical manifestation of RA. This hypothesis warrants further investigation.
format	article
author	Klára Prajzlerová Olga Kryštůfková Petra Hánová Veronika Horváthová Monika Gregová Karel Pavelka Jiří Vencovský Ladislav Šenolt Mária Filková
author_facet	Klára Prajzlerová Olga Kryštůfková Petra Hánová Veronika Horváthová Monika Gregová Karel Pavelka Jiří Vencovský Ladislav Šenolt Mária Filková
author_sort	Klára Prajzlerová
title	High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis
title_short	High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis
title_full	High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis
title_fullStr	High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis
title_full_unstemmed	High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis
title_sort	high mir-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/34a12d51cbab4668bad29802f3f1eafb
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High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritis

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