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肿瘤坏死因子-α诱导的miR-155调节类风湿性滑膜成纤维细胞中的白细胞介素-6信号通路。

TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts.

作者信息

Migita Kiyoshi, Iwanaga Nozomi, Izumi Yasumori, Kawahara Chieko, Kumagai Kenji, Nakamura Tadashi, Koga Tomohiro, Kawakami Atsushi

机构信息

Department of Rheumatology, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan.

Department of Rheumatology and Clinical Research Center, NHO Nagasaki Medical Center, Omura, Nagasaki, Japan.

出版信息

BMC Res Notes. 2017 Aug 14;10(1):403. doi: 10.1186/s13104-017-2715-5.

DOI:10.1186/s13104-017-2715-5
PMID:28807007
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5556669/
Abstract

BACKGROUND

MicroRNAs (miRNAs) are important regulators of a variety of inflammatory mediators. The present study was undertaken to elucidate the role of miRNAs in the rheumatoid cytokine network.

METHODS

We analyzed miRNA expression in rheumatoid synovial fibroblasts (RASFs). miRNA array-based screening was used to identify miRNAs differentially expressed between tumor necrosis factor-α (TNF-α)-activated RASFs and untreated RASFs. Transfection of RASFs with miR-155 was used to analyze the function of miR-155. Real-time polymerase chain reaction (PCR) was used to measure the levels of miR-155 in RASFs.

RESULTS

miRNA microarray analysis revealed that miR-155-5p was the most highly induced miRNA in TNF-α-stimulated RASFs. TNF-α-induced miR-155 expression in RASFs was time-dependent and TNFα dose-dependent, whereas, IL-6 stimulation did not affect miR-155 expression in RASFs. Transfection of miR-155 mimics into RASFs resulted in the decrease JAK2/STAT3 phosphorylation in IL-6-treated RASFs.

CONCLUSIONS

The current results demonstrate that TNF-α modulated miRNA expressions in RASFs. Our data showed that miR-155, which is highly induced by TNF-α stimulation, inhibits IL-6-mediated JAK2/STAT3 activation in RASFs. These findings suggest that miR-155 contributes to the cross-regulation between TNF-α and IL-6-mediated inflammatory pathways in RA.

摘要

背景

微小RNA（miRNA）是多种炎症介质的重要调节因子。本研究旨在阐明miRNA在类风湿细胞因子网络中的作用。

方法

我们分析了类风湿性滑膜成纤维细胞（RASF）中的miRNA表达。基于miRNA芯片的筛选用于鉴定肿瘤坏死因子-α（TNF-α）激活的RASF与未处理的RASF之间差异表达的miRNA。用miR-155转染RASF以分析miR-155的功能。实时聚合酶链反应（PCR）用于测量RASF中miR-155的水平。

结果

miRNA芯片分析显示，miR-155-5p是TNF-α刺激的RASF中诱导程度最高的miRNA。TNF-α诱导RASF中miR-155的表达呈时间依赖性和TNFα剂量依赖性，而IL-6刺激不影响RASF中miR-155的表达。将miR-155模拟物转染到RASF中导致IL-6处理的RASF中JAK2/STAT3磷酸化降低。

结论

目前的结果表明TNF-α调节RASF中的miRNA表达。我们的数据表明，TNF-α刺激高度诱导的miR-155抑制RASF中IL-6介导的JAK2/STAT3激活。这些发现表明miR-155有助于类风湿关节炎中TNF-α和IL-6介导的炎症途径之间的交叉调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a59/5556669/50294bddfe90/13104_2017_2715_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a59/5556669/342d596452fb/13104_2017_2715_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a59/5556669/899c900e23ca/13104_2017_2715_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a59/5556669/50294bddfe90/13104_2017_2715_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a59/5556669/342d596452fb/13104_2017_2715_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a59/5556669/899c900e23ca/13104_2017_2715_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a59/5556669/50294bddfe90/13104_2017_2715_Fig3_HTML.jpg

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