論文 - 詳細
| RRC ID | 65634 |
|---|---|
| 著者 | Moriya N, Shibasaki S, Karasaki M, Iwasaki T. |
| タイトル | The Impact of MicroRNA-223-3p on IL-17 Receptor D Expression in Synovial Cells. |
| ジャーナル | PLoS One |
| Abstract |
OBJECTIVE:Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting joints. Elevated plasma levels of microRNA-223-3p (miR-223-3p) in patients with RA are implicated in the pathogenesis of the disease. This study aimed to analyze the functional role of miR-223-3p in the pathogenesis of RA by overexpressing miR-223-3p in synovial cell lines. METHODS:Arthritis was induced in the RA model of SKG mice by injection of ß-glucan. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Plasma levels of miRNA were determined by panel real-time PCR analysis. Target genes of the differentially expressed miRNAs in SKG mice were analyzed using miRNA target prediction algorithms. The dual-luciferase reporter system was used to evaluate the relationship between miR-223-3p and IL-17 receptor D (IL-17RD). The activity of miR-223-3p was analyzed by transfection of plasmid vectors overexpressing miR-223-3p into IL-17RD-expressing NIH3T3 and MH7A cell lines. Il6 and Il17rd mRNA expression was analyzed by quantitative real-time PCR. IL-17RD protein expression was analyzed by western blot analysis. RESULTS:We identified 17 upregulated miRNAs (fold change > 2.0) in plasma of SKG mice injected with ß-glucan relative to untreated SKG mice. Il17rd was identified as the candidate target gene of miR-223-3p using five miRNA target prediction algorithms. The transfection of plasmid vectors overexpressing miR-223-3p into NIH3T3 and MH7A cells resulted in the downregulation of Il17rd expression and upregulation of Il6 expression. Expression of miR-223-3p and Il6 mRNA in MH7A cells was upregulated; however, that of Il17rd mRNA was downregulated following TNF-α stimulation. IL-17RD expression in synovial tissues from SKG mice and RA patients was inversely correlated with the severity of arthritis. CONCLUSION:This study is the first to demonstrate that miR-223-3p downregulates IL-17RD in both mouse and human cells; miR-223-3p may contribute to the pathogenesis of RA by downregulating the expression of IL-17RD and upregulating that of IL-6 in synovial cells. |
| 巻・号 | 12(1) |
| ページ | e0169702 |
| 公開日 | 2017-1-1 |
| DOI | 10.1371/journal.pone.0169702 |
| PII | PONE-D-16-35453 |
| PMID | 28056105 |
| PMC | PMC5215929 |
| MeSH | Animals Arthritis, Rheumatoid / metabolism Blotting, Western Female Humans Interleukin-6 / metabolism Mice MicroRNAs / genetics MicroRNAs / metabolism* NIH 3T3 Cells Real-Time Polymerase Chain Reaction Receptors, Interleukin-17 / genetics Receptors, Interleukin-17 / metabolism* Synovial Membrane / cytology* Synovial Membrane / drug effects Synovial Membrane / metabolism Tumor Necrosis Factor-alpha / pharmacology beta-Glucans / pharmacology |
| IF | 2.74 |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |