Deregulation of microRNA expression in monocytes and CD4+ T lymphocytes from patients with axial spondyloarthritis

Fogel, O.; Tinggaard, Andreas Bugge; Fagny, Maud; Sigrist, Nelly; Roché, Elodie; Leclere, Laurence; Deleuze, Jean‐François; Batteux, Frédéric; Dougados, Maxime; Miceli‐Richard, Corinne; Tost, Jörg

doi:10.1186/s13075-019-1829-7

“…Recently, differential expression of miR-2137 was observed in bone marrow-derived macrophages after infection with Porphyromonas Gingivalis bacteria (23), and inhibiting miR-2137 increased expression of the anti-inflammatory cytokine IL-10 suggesting that miR-2137 may be pro-inflammatory following O3 exposure. We also observed an O3-induced upregulation of EV miR-126-3p, a well-studied pro-inflammatory miRNA (15). miR-126-3p is also upregulated in inflammatory bowel disease (IBD), in which it targets nuclear factor-kappaB inhibitor alpha (IκB) (14,54) and impairs intestinal epithelial barrier function (7).…”

Section: Discussionmentioning

confidence: 80%

Ozone-induced changes in murine lung extracellular vesicle number and small RNA content

Smith

¹

,

Tovar

²

,

Kanke

³

et al. 2020

Preprint

0

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Inhalation exposure to ozone (O3) causes adverse respiratory health effects that result from airway inflammation, a complex response mediated by changes to airway cellular transcriptional programs. These programs may be regulated in part by a subset of microRNAs transferred between cells (e.g. epithelial cells and macrophages) via extracellular vesicles (EV miRNA). To explore this, we exposed female C57BL/6J mice to filtered air (FA), 1, or 2 ppm O3 by inhalation and collected bronchoalveolar lavage fluid (BALF) 21 hours later for markers of airway inflammation, EVs, and EV miRNA. Both concentrations of O3 significantly increased markers of inflammation (neutrophils and total protein) and the number of EVs in the BALF.Using high-throughput small RNA sequencing, we identified several differentially expressed (DE) BALF EV miRNAs after 1 ppm (16 DE miRNAs) and 2 ppm (99 DE miRNAs) O3 versus FA exposure. O3 concentration response patterns in EV miRNA expression were apparent, particularly for the two most highly expressed (miR-2137 and miR-126-3p) and lowly expressed (miR-378-3p and miR-351-5p) miRNAs. Integrative analysis of EV miRNA expression and airway cellular mRNA expression identified EV miR-22-3p as a candidate regulator of transcriptomic responses to O3 in airway macrophages. In contrast, we did not identify candidate miRNA regulators of mRNA expression data from conducting airways (predominantly composed of epithelial cells). In summary, our data show that O3 exposure alters EV release and EV miRNA expression, suggesting that further investigation of EVs may provide insight into their effects on airway macrophage function and other mechanisms of O3-induced respiratory inflammation. enhanced antigen presentation activity (32). Epithelial cell barrier dysfunction and damage are evidenced by the presence of an intra-alveolar, albumin-rich exudate following O3 exposure (21). Shared functional responses, albeit differing with respect to timing and precise mediators, include the release of pro-inflammatory cytokines (e.g. IL-6 (11), IL-1 family (37), TNFα (13)) and altered production/activity of other proteins (e.g. surfactant (20), metallothionein (24), matrix metalloproteinases (55)), and small molecules (e.g. antioxidants (5), eicosanoids (11), specialized pro-resolving lipid mediators (29)).Underlying the functional cellular responses of airway macrophage and epithelial cells to O3 are alterations in inflammatory, immune, and oxidative stress response gene expression programs. Transcriptomic and proteomic studies have better illuminated the landscape of gene expression responses to O3, revealing the involvement of the protease/anti protease system (28), heat shock proteins (39), and NRF2 (8) and NF-kB family transcription factors (26). Novel O3responsive genes have also been discovered recently, including oxytocin receptor (Oxtr) in conducting airways and hairy enhancer of split 1 (Hes1) in airway macrophages (51). Although the gene expression landscape of the airway response to O3 is becoming clearer, the pr...

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“…Deregulation of hsa-miR-28-5p is related to rheumatic diseases, such as axial spondyloarthritis and rheumatoid arthritis. 49,50 Herein, we first found that hsa-miR-28-5p was up-regulated in osteonecrosis of the femoral head. In addition, the down-regulated RELA proto-oncogene, NF-kB subunit (RELA, also called p65) was one of the targets of hsa-miR-28-5p.…”

Section: Discussionmentioning

confidence: 96%

Identifying the Potential Differentially Expressed miRNAs and mRNAs in Osteonecrosis of the Femoral Head Based on Integrated Analysis

Hao

¹

,

Lü

²

,

Zhang

³

et al. 2021

CIA

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Purpose Osteonecrosis of the femoral head is a common disease of the hip that leads to severe pain or joint disability. We aimed to identify potential differentially expressed miRNAs and mRNAs in osteonecrosis of the femoral head. Methods The data of miRNA and mRNA were firstly downloaded from the database. Secondly, the regulatory network of miRNAs–mRNAs was constructed, followed by function annotation of mRNAs. Thirdly, an in vitro experiment was applied to validate the expression of miRNAs and targeted mRNAs. Finally, GSE123568 dataset was used for electronic validation and diagnostic analysis of targeted mRNAs. Results Several regulatory interaction pairs between miRNA and mRNAs were identified, such as hsa-miR-378c-WNT3A/DACT1/CSF1, hsa-let-7a-5p-RCAN2/IL9R, hsa-miR-28-5p-RELA, hsa-miR-3200-5p-RELN, and hsa-miR-532-5p-CLDN18/CLDN10. Interestingly, CLDN10, CLDN18, CSF1, DACT1, IL9R, RCAN2, RELN, and WNT3A had the diagnostic value for osteonecrosis of the femoral head. Wnt signaling pathway (involved WNT3A), chemokine signaling pathway (involved RELA), focal adhesion and ECM-receptor interaction (involved RELN), cell adhesion molecules (CAMs) (involved CLDN18 and CLDN10), cytokine–cytokine receptor interaction, and hematopoietic cell lineage (involved CSF1 and IL9R) were identified. Conclusion The identified differentially expressed miRNAs and mRNAs may be involved in the pathology of osteonecrosis of the femoral head.

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“…In AS, immunopathogenesis and bone remodeling are the mainstays involved in disease pathogenesis. Accordingly, miRNAs might be implicated in AS diagnostic, prognostic, and therapeutic processes [8,10].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the important role of circulating miRNAs in AS pathogenesis has been explored [8]. T cells and peripheral blood mononuclear cells (PBMCs) of AS patients have shown an altered miRNA expression which is involved in specific pathways in the disease pathogenesis [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the important role of circulating miRNAs in AS pathogenesis has been explored [8]. T cells and peripheral blood mononuclear cells (PBMCs) of AS patients have shown an altered miRNA expression which is involved in specific pathways in the disease pathogenesis [8,9]. Low expression of miRNA-451a and miR-150-5p with high expression of miRNA46a-5p, miRNA-125a, miR-151a-3p, and miR-22-3p was observed in PBMCs of AS patients [10].…”

Section: Introductionmentioning

confidence: 99%

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miRNA-451a and miRNA-125a Expression Levels in Ankylosing Spondylitis: Impact on Disease Diagnosis, Prognosis, and Outcomes

Fotoh

¹

,

Noreldin

²

,

Rizk

³

et al. 2020

Journal of Immunology Research

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Background. Early diagnosis of ankylosing spondylitis (AS) is yet not elucidated, with a potential diagnostic glance of microRNAs (miRNAs). Aim. Study the expression profile of miRNA-451a and miRNA-125a in AS patients and their impact on disease activity and prognosis. Methods. A cross-sectional study included 55 AS patients diagnosed according to modified New York criteria in 1984 with 55 matched healthy controls. History, clinical examination, and disease activity assessment with Bath ankylosing spondylitis disease activity index (BASDAI) were done. Full laboratory and radiological assessment along with expression profile of m iRNA-451a and miRNA-125a were tabulated and analyzed. Results. Higher expression levels of miRNA-125a and lower of miRNA-451a in AS patients compared to controls. Furthermore, miRNA-125a expression was high in active AS patients compared to inactive patients and controls ( 7.0 ± 3.4 vs. 4.1 ± 2.1 vs. 2.6 ± 0.6 , p < 0.001 , respectively). miRNA-451a was significantly lower in active AS patients compared to inactive patients and controls ( 2.2 ± 1.1 vs. 4.1 ± 2.3 vs. 7.1 ± 4.5 , respectively). Both miRNAs (miRNA-125a and miRNA-451a) had evident accuracy for AS diagnosis with areas under the curve (AUC) of 0.788 and 0.802, respectively. miRNA-125a had potential impact on AS activity with AUC of 0.777. Plasma levels of both miRNAs were able to distinguish AS patients with structural damage with AUCs 0.775 and 0.692, respectively. Conclusions. Both miRNA-451a and miRNA-125a were found to be of great value as sensitive noninvasive diagnostic, prognostic, and disease burden biomarker of AS patients in Egypt with suggested further studies for future therapeutic implications.

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Deregulation of microRNA expression in monocytes and CD4+ T lymphocytes from patients with axial spondyloarthritis

Cited by 27 publications

References 76 publications

Ozone-induced changes in murine lung extracellular vesicle number and small RNA content

Ozone-induced changes in murine lung extracellular vesicle number and small RNA content

Identifying the Potential Differentially Expressed miRNAs and mRNAs in Osteonecrosis of the Femoral Head Based on Integrated Analysis

miRNA-451a and miRNA-125a Expression Levels in Ankylosing Spondylitis: Impact on Disease Diagnosis, Prognosis, and Outcomes

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