Glässer's disease, caused by Haemophilus parasuis (H. parasuis), is associated with vascular damage and vascular inflammation in pigs. Therefore, early assessment and treatment are essential to control the inflammatory disorder. MicroRNAs have been shown to be involved in the vascular pathology. Baicalin has important pharmacological functions, including anti-inflammatory, antimicrobial and antioxidant effects. In this study, we investigated the changes of microRNAs in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis and the effect of baicalin in this model by utilizing high-throughput sequencing. The results showed that 155 novel microRNAs and 76 differentially expressed microRNAs were identified in all samples. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the target genes of the differentially expressed microRNAs demonstrated that regulation of actin cytoskeleton, focal adhesion, ECM-receptor interaction, bacterial invasion of epithelial cells, and adherens junction were the most interesting pathways after PAVECs were infected with H. parasuis. In addition, when the PAVECs were pretreated with baicalin, mismatch repair, peroxisome, oxidative phosphorylation, DNA replication, and ABC transporters were the most predominant signaling pathways. STRING analysis showed that most of the target genes of the differentially expressed microRNAs were associated with each other. The expression levels of the differentially expressed microRNAs were negatively co-regulated with their target genes' mRNA following pretreatment with baicalin in the H. parasuis-induced PAVECs using co-expression networks analysis. This is the first report that microRNAs might have key roles in inflammatory damage of vascular tissue during H. parasuis infection. Baicalin regulated the microRNAs changes in the PAVECs following H. parasuis infection, which may represent useful novel targets to prevent or treat H. parasuis infection.

译文

由副猪嗜血杆菌 (H. parasuis) 引起的gl ä sser病,与猪的血管损伤和血管炎症有关。因此,早期评估和治疗对于控制炎症性疾病至关重要。已显示MicroRNAs参与血管病理。黄芩苷具有重要的药理作用,包括抗炎、抗菌和抗氧化作用。在这项研究中,我们利用高通量测序研究了副猪H. parasuis诱导的猪主动脉血管内皮细胞 (PAVECs) 中microrna的变化以及黄芩苷在该模型中的作用。结果表明,在所有样品中鉴定出155种新的microrna和76种差异表达的microrna。随后,《京都基因与基因组百科全书》 (KEGG) 对差异表达的microRNAs靶基因的富集分析表明,调控肌动蛋白细胞骨架、黏着斑、ECM-受体相互作用、细菌侵袭上皮细胞、在PAVECs感染副猪H.后,粘附性连接是最有趣的途径。此外,当用黄芩苷预处理PAVECs时,错配修复,过氧化物酶体,氧化磷酸化,DNA复制和ABC转运蛋白是最主要的信号通路。串分析表明,差异表达的microrna的大多数靶基因相互关联。使用共表达网络分析,在副猪H. parasuis诱导的PAVECs中用黄芩苷预处理后,差异表达的microrna的表达水平与其靶基因的mRNA呈负共调节。这是首次报道microrna可能在副猪H. parasuis感染期间血管组织的炎症损伤中起关键作用。黄芩苷调节副猪H感染后PAVECs中microRNAs的变化,这可能是预防或治疗副猪H感染的有用新靶标。

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