Induction of microRNA-155 during Helicobacter pylori Infection and Its Negative Regulatory Role in the Inflammatory Response
Induction of microRNA-155 during Helicobacter pylori Infection and Its Negative Regulatory Role in the Inflammatory Response
复制标题
幽门螺杆菌感染过程中 microRNA-155 的诱导及其在炎症反应中的负调节作用
DOI：
10.1086/605443
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发表时间：
2009-09-15
影响因子：
6.4
通讯作者：
Zou, Quan-Ming
中科院分区：
文献类型：
--
作者：
Xiao, Bin;Liu, Zhen;Zou, Quan-Ming
背景microRNA（miRNAs）是一类在转录后水平调控基因表达的非编码小RNA。H.幽门螺杆菌是人类胃粘膜的主要致病菌。迄今为止，miRNAs在H.尚未探讨过幽门螺杆菌感染。方法。H. pylori感染通过使用微阵列和定量逆转录聚合酶链反应进行分析。通过荧光素酶法和Western blot鉴定miR-155的潜在靶点。启动子分析和抑制剂实验用于研究参与miR-155诱导的途径。通过过表达和抑制miR-155来检测miR-155的功能。H. pylori感染可增加胃上皮细胞系和胃粘膜组织中miR-155的表达，miR-155的诱导需要核因子-κ B（NF-κ B B）和激活蛋白-1（AP-1）通路。miR-155可下调I κ B激酶A、Sma和Mad-related protein 2（SMAD 2）和Fas相关死亡结构域蛋白。此外，miR-155的过表达可负性调节白细胞介素-8和生长相关癌基因-α的释放。这项研究首次描述了miR-155在H. pylori感染，miR-155可能作为一种新的负调节因子，有助于微调H.幽门感染
Background. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at posttranscriptional level. H. pylori is a major human pathogenic bacterium in gastric mucosa. To date, the role of miRNAs in response to H. pylori infection has not been explored.Methods. The expression profile of cellular miRNAs during H. pylori infection was analyzed by using microarray and quantitative reverse-transcriptase polymerase chain reaction. The potential target of miR-155 was identified by luciferase assay and Western blot. Promoter analysis and inhibitor experiment were used to investigate the pathway involved in the induction of miR-155. Examination of miR-155 function was performed by overexpression and inhibition of miR-155.Results. H. pylori was able to increase the miR-155 expression in gastric epithelial cell lines and gastric mucosal tissues, and nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) pathway were required for the induction of miR-155. miR-155 may down-regulate I kappa B kinase epsilon, Sma- and Mad-related protein 2 (SMAD2), and Fas-associated death domain protein. Furthermore, the overexpression of miR-155 negatively regulated the release of interleukin-8 and growth-related oncogene-alpha.Conclusions. This study provides the first description of increased expression of miR-155 in H. pylori infection, and miR-155 may function as novel negative regulator that help to fine-tune the inflammation response of H. pylori infection.