Expression of microRNA‐146 in rheumatoid arthritis synovial tissue

Abstract

Objective Several microRNA, which are ∼22‐nucleotide noncoding RNAs, exhibit tissue‐specific or developmental stage–specific expression patterns and are associated with human diseases. The objective of this study was to identify the expression pattern of microRNA‐146 (miR‐146) in synovial tissue from patients with rheumatoid arthritis (RA). Methods The expression of miR‐146 in synovial tissue from 5 patients with RA, 5 patients with osteoarthritis (OA), and 1 normal subject was analyzed by quantitative reverse transcription–polymerase chain reaction (RT‐PCR) and by in situ hybridization and immunohistochemistry of tissue sections. Induction of miR‐146 following stimulation with tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT‐PCR. Results Mature miR‐146a and primary miR‐146a/b were highly expressed in RA synovial tissue, which also expressed TNFα, but the 2 microRNA were less highly expressed in OA and normal synovial tissue. In situ hybridization showed primary miR‐146a expression in cells of the superficial and sublining layers in synovial tissue from RA patients. Cells positive for miR‐146a were primarily CD68+ macrophages, but included several CD3+ T cell subsets and CD79a+ B cells. Expression of miR‐146a/b was markedly up‐regulated in RASFs after stimulation with TNFα and IL‐1β. Conclusion This study shows that miR‐146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFα and IL‐1β. Further studies are required to elucidate the function of miR‐146 in these tissues.

Epigenetics, aging, and autoimmunity

“…For example, reducing the activity of C. elegans linage 4 (lin-4) miRNA shortens lifespan, whereas overexpression of lin-4 extends lifespan (55,56). Interestingly, two groups reported that the expression pattern of miR-155 and miR-146 miRNAs is altered in synovial tissue in RA, suggesting a potential role of miRNA in the pathogenesis of other disorders acquired with age (57,58).…”

miR-146a negatively regulates NK cell functions via STAT1 signaling

“…Elevated miR-146 expression levels, which are likely to reflect the infiltration of inflammatory cells and increased levels of mediators tumor necrosis factor (TNF)-α and IL-1β, were found in tissues related to chronic inflammatory diseases such as psoriasis and rheumatoid arthritis. 17 In addition, miR-146a is an important modulator of innate immune cell differentiation and function, as well as adaptive immunity. In monocytes, miR-146a attenuates TLR4 signaling and contributes to endotoxin tolerance by targeting TRAF6 and IRAK1.…”

A plasma microRNA signature as a biomarker for acquired aplastic anemia

“…10 Dysregulation of miRNAs can lead to autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). 11,12 Although miRNA regulation of each target results in small changes in gene expression, the network activity of miRNAs affecting hundreds of genes simultaneously can produce dramatic changes in cell behavior. 13 We have recently reported that downregulation of miR-126-3p and miR-145-5p promotes CD4 + and CD8 + T-cell activation by increasing MYC and PIK3R2 expression levels in AA patients.…”