Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation.
Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation.
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胰腺腺泡细胞利用 miRNA 作为细胞间通讯的介质来参与胰腺炎相关巨噬细胞激活的调节
DOI：
10.1155/2016/6340457
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发表时间：
2016
影响因子：
4.6
通讯作者：
Xue D
中科院分区：
文献类型：
--
作者：
Zhao Y;Wang H;Lu M;Qiao X;Sun B;Zhang W;Xue D
巨噬细胞活化在急性胰腺炎的炎症反应中起重要作用。在本研究中，AR 42 J胰腺腺泡细胞的激活诱导牛磺石胆酸盐处理。结果显示，与未用牛磺石胆酸盐处理的培养液相比，来自活化的AR 42 J细胞的培养液显著增强了巨噬细胞中的NFκB活化。此外，与缺乏外来体的上清液级分相比，从富含外来体的培养基的超离心获得的沉淀物在活化巨噬细胞方面明显更有效。结果表明，外泌体携带的介质在巨噬细胞活化中起重要作用。提取外泌体miRNA并使用微阵列进行检查。共鉴定出115个差异表达的miRNAs，其中30个表达上调，85个表达下调。利用TargetScan、米兰达和PicTar软件程序预测差异表达miRNA的靶基因。对推定的靶基因进行KEGG功能分析。靶基因的功能主要集中在MAPK通路中。具体而言，靶基因通过TRAF 6-TAB 2-TAK 1-NIK/IKK-NFκB途径调节巨噬细胞活化。miRNAs及其预测的靶mRNA作为信号转导的介导因子，调控MAPK信号转导的各个环节。
Macrophage activation plays an important role in the inflammatory response in acute pancreatitis. In the present study, the activation of AR42J pancreatic acinar cells was induced by taurolithocholate treatment. The results showed that the culture medium from the activated AR42J cells significantly enhanced NFκB activation in the macrophages compared to that without taurolithocholate treatment. Additionally, the precipitates obtained from ultracentrifugation of the culture media that were rich in exosomes were markedly more potent in activating macrophages compared with the supernatant fraction lacking exosomes. The results indicated that the mediators carried by the exosomes played important roles in macrophage activation. Exosomal miRNAs were extracted and examined using microarrays. A total of 115 differentially expressed miRNAs were identified, and 30 showed upregulated expression, while 85 displayed downregulated expression. Target genes of the differentially expressed miRNAs were predicted using TargetScan, MiRanda, and PicTar software programs. The putative target genes were subjected to KEGG functional analysis. The functions of the target genes were primarily enriched in MAPK pathways. Specifically, the target genes regulated macrophage activation through the TRAF6-TAB2-TAK1-NIK/IKK-NFκB pathway. As the mediators of signal transduction, miRNAs and their predicted target mRNAs regulate every step in the MAPK pathway.