Department of Veterinary Clinical and Animal Sciences, Section of Anatomy, Cell Biology, Genetics and Bioinformatics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.
BMC Genomics. 2012 Sep 6;13:459. doi: 10.1186/1471-2164-13-459.
MicroRNAs (miRNAs) are a class of non-protein-coding genes that play a crucial regulatory role in mammalian development and disease. Whereas a large number of miRNAs have been annotated at the structural level during the latest years, functional annotation is sparse. Actinobacillus pleuropneumoniae (APP) causes serious lung infections in pigs. Severe damage to the lungs, in many cases deadly, is caused by toxins released by the bacterium and to some degree by host mediated tissue damage. However, understanding of the role of microRNAs in the course of this infectious disease in porcine is still very limited.
In this study, the RNA extracted from visually unaffected and necrotic tissue from pigs infected with Actinobacillus pleuropneumoniae was subjected to small RNA deep sequencing. We identified 169 conserved and 11 candidate novel microRNAs in the pig. Of these, 17 were significantly up-regulated in the necrotic sample and 12 were down-regulated. The expression analysis of a number of candidates revealed microRNAs of potential importance in the innate immune response. MiR-155, a known key player in inflammation, was found expressed in both samples. Moreover, miR-664-5p, miR-451 and miR-15a appear as very promising candidates for microRNAs involved in response to pathogen infection.
This is the first study revealing significant differences in composition and expression profiles of miRNAs in lungs infected with a bacterial pathogen. Our results extend annotation of microRNA in pig and provide insight into the role of a number of microRNAs in regulation of bacteria induced immune and inflammatory response in porcine lung.
MicroRNAs(miRNAs)是一类非编码基因,在哺乳动物的发育和疾病中发挥着关键的调控作用。尽管近年来在结构水平上注释了大量的 miRNAs,但功能注释仍然很少。胸膜肺炎放线杆菌(APP)会导致猪的肺部严重感染。细菌释放的毒素以及在一定程度上宿主介导的组织损伤会导致肺部严重受损,在许多情况下是致命的。然而,对于 miRNA 在这种猪传染性疾病过程中的作用的理解仍然非常有限。
在这项研究中,从感染胸膜肺炎放线杆菌的肉眼未见影响和坏死组织中提取 RNA,进行小 RNA 深度测序。我们在猪中鉴定了 169 个保守和 11 个候选新的 microRNAs。其中,17 个在坏死样本中显著上调,12 个下调。对一些候选物的表达分析揭示了在先天免疫反应中具有潜在重要性的 microRNAs。miR-155 是炎症的已知关键调节因子,在两个样本中均有表达。此外,miR-664-5p、miR-451 和 miR-15a 似乎是参与病原体感染反应的非常有前途的候选物。
这是首次揭示细菌感染肺部的 miRNA 组成和表达谱存在显著差异的研究。我们的研究结果扩展了猪 miRNA 的注释,并深入了解了一些 miRNA 在调节猪肺部细菌诱导的免疫和炎症反应中的作用。