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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84004-3 |
| _version_ | 1818996339347816448 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T21:28:10Z |
| format | Article |
| id | doaj.art-34a12d51cbab4668bad29802f3f1eafb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:28:10Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-34a12d51cbab4668bad29802f3f1eafb2022-12-21T19:26:07ZengNature PortfolioScientific Reports2045-23222021-02-011111910.1038/s41598-021-84004-3High miR-451 expression in peripheral blood mononuclear cells from subjects at risk of developing rheumatoid arthritisKlára Prajzlerová0Olga Kryštůfková1Petra Hánová2Veronika Horváthová3Monika Gregová4Karel Pavelka5Jiří Vencovský6Ladislav Šenolt7Mária Filková8Institute of RheumatologyInstitute of RheumatologyInstitute of RheumatologyInstitute of RheumatologyInstitute of RheumatologyInstitute of RheumatologyInstitute of RheumatologyInstitute of RheumatologyInstitute of RheumatologyAbstract 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.https://doi.org/10.1038/s41598-021-84004-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-84004-3 |
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