RETRACTED: Elevated microRNA-125b promotes inflammation in rheumatoid arthritis by activation of NF-κB pathway (Retracted Article)

被引:41
作者
Zhang, Bo [1 ]
Wang, Li-Song [2 ]
Zhou, Yu-Hu [3 ]
机构
[1] Weinan Cent Hosp, Weinan 714000, Shaanxi, Peoples R China
[2] Shangluo Cent Hosp, Dept Orthoped 2, Shangluo 726300, Shaanxi, Peoples R China
[3] Yanan Univ, Affiliated Hosp, Dept Orthoped, 43 Beida St, Yanan 716000, Shaanxi, Peoples R China
关键词
Rheumatoid arthritis; MicroRNA-125b; Pro-inflammatory cytokines; Nuclear factor kappa B pathway; NECROSIS-FACTOR-ALPHA; SYNOVIAL FIBROBLASTS; TNF-ALPHA; ALTERED EXPRESSION; CYTOKINES; MIR-125B; DISEASE; OSTEOARTHRITIS; INTERLEUKIN-1; BLOCKING;
D O I
10.1016/j.biopha.2017.07.042
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
microRNA-125b(miR-125b) has been reported to be increased in rheumatoid arthritis (RA). However, the role of miR-125b in RA remains to be fully elucidated. We aimed to explore the functional role of miR125b in RA, as well as the underlying mechanism. The expression of miR-125b in serum and synovial tissues of patients with RA and healthy controls was confirmed. In addition, the levels of miR-125b in lipopolysaccharide (LPS)-stimulated fibroblast-like synoviocytes (FLS) were also measured. FLS were transfected with miR-125b mimic, antisense oligonucleotides (ASO)-miR-125b, pcDNA-inhibitor of NF kappa B (I kappa B)-a or corresponding controls, and then stimulated with LPS or incubated with nuclear factor kappa B (NF-kappa B) inhibitors pyrrolidine dithiocarbamate (PDTC). The effects of miR-125b abnormal expression on pro- inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)- 6 and IL-1 beta and NF-kappa B pathway key factors phospho-p65 (p-p65) and I kappa B- a were assessed. Pearson correlation analysis was performed to assess the relationship between miR-125b expression and proinflammatory cytokines expression. Result showed that, the levels of miR-125b were significantly increased in RA serum and synovial tissues, as well as in LPS- stimulated FLS (P < 0.01). miR-125b overexpression statistically increased the expression of TNF- a, IL-6, IL-1 beta and p-p65 (P < 0.05 or P < 0.01), but markedly decreased I kappa B-a (P < 0.05). Contrary results were obtained by miR-125b downregulation. Additionally, there were strong positive relationships between miR-125b and TNF-a (R-2 = 0.7569, P < 0.000), IL-6 (R-2 = 0.8479, P < 0.000), and IL-1 beta (R-2 = 0.8037, P < 0.000). Moreover, the upregulated levels of pro- inflammatory cytokines were markedly decreased by PDTC (P < 0.01) and further downregulated by co-transfection with pcDNA-I kappa B-a (P < 0.01). In conclusion, our results suggest that elevated miR- 125b promotes inflammation in RA by activation of NF-kappa B pathway. (C) 2017 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:1151 / 1157
页数:7
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