Academic Journal
MicroRNA-27a-3p enhances the inflammatory phenotype of Juvenile Idiopathic Arthritis fibroblast-like synoviocytes
Title: | MicroRNA-27a-3p enhances the inflammatory phenotype of Juvenile Idiopathic Arthritis fibroblast-like synoviocytes |
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Authors: | Claire H. Bullock, Sarah M. McAlpine, Sarah E. Roberts, Beata Derfalvi |
Source: | Pediatric Rheumatology Online Journal, Vol 21, Iss 1, Pp 1-12 (2023) |
Publisher Information: | BMC, 2023. |
Publication Year: | 2023 |
Collection: | LCC:Pediatrics LCC:Diseases of the musculoskeletal system |
Subject Terms: | Fibroblast-like synoviocytes, Inflammation, Juvenile idiopathic arthritis, microRNA, Synovial fluid, Pediatrics, RJ1-570, Diseases of the musculoskeletal system, RC925-935 |
More Details: | Abstract Background Juvenile Idiopathic Arthritis (JIA) is the most prevalent chronic pediatric rheumatic disorder. In joints of JIA patients, aggressive phenotypic changes in fibroblast-like synoviocytes (FLS) of the synovial lining play a key role in inflammation. MicroRNAs are dysregulated in rheumatoid arthritis and JIA, including miR-27a-3p. However, it is not understood if miR-27a-3p, enriched in JIA synovial fluid (SF) and leukocytes, alters FLS function. Methods Primary JIA FLS cells were transfected with a miR-27a-3p mimic or a negative control microRNA (miR-NC) and stimulated with pooled JIA SF or inflammatory cytokines. Viability and apoptosis were analyzed by flow cytometry. Proliferation was evaluated using a 3H-thymidine incorporation assay. Cytokine production was assessed by qPCR and ELISA. Expression of TGF-β pathway genes was determined using a qPCR array. Results MiR-27a-3p was constitutively expressed in FLS. Overexpression of miR-27a-3p caused increased interleukin-8 secretion in resting FLS, and interleukin-6 was elevated in SF-activated FLS compared to miR-NC. Furthermore, stimulation with pro-inflammatory cytokines augmented FLS proliferation in miR-27a-3p-transfected FLS relative to miR-NC. Expression of multiple TGF-β pathway genes was modulated by overexpression of miR-27a-3p. Conclusions MiR-27a-3p significantly contributes to FLS proliferation and cytokine production, making it a potential candidate for epigenetic therapy that targets FLS in arthritis. |
Document Type: | article |
File Description: | electronic resource |
Language: | English |
ISSN: | 1546-0096 |
Relation: | https://doaj.org/toc/1546-0096 |
DOI: | 10.1186/s12969-023-00833-8 |
Access URL: | https://doaj.org/article/f0f8b3a5436f42c5be5a32a6c623de2d |
Accession Number: | edsdoj.f0f8b3a5436f42c5be5a32a6c623de2d |
Database: | Directory of Open Access Journals |
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ISSN: | 15460096 |
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DOI: | 10.1186/s12969-023-00833-8 |
Published in: | Pediatric Rheumatology Online Journal |
Language: | English |