Ghafouri Farzad, Dehghanian Reyhan Vahid, Sadeghi Mostafa, Miraei-Ashtiani Seyed Reza, Kastelic John P, Barkema Herman W, Shirali Masoud
Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj 77871-31587, Iran.
Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Noncoding RNA. 2024 Jun 28;10(4):38. doi: 10.3390/ncrna10040038.
Paratuberculosis or Johne's disease (JD), a chronic granulomatous gastroenteritis caused by subsp. (MAP), causes huge economic losses and reduces animal welfare in dairy cattle herds worldwide. At present, molecular mechanisms and biological functions involved in immune responses to MAP infection of dairy cattle are not clearly understood. Our purpose was to integrate transcriptomic profiles and competing endogenous RNA (ceRNA) network analyses to identify key messenger RNAs (mRNAs) and regulatory RNAs involved in molecular regulation of peripheral blood mononuclear cells (PBMCs) for MAP infection in dairy cattle. In total, 28 lncRNAs, 42 miRNAs, and 370 mRNAs were identified by integrating gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In this regard, we identified 21 hub genes (, , , , , , , , , , , , , , , , , , , , and ) involved in MAP infection. Furthermore, eight candidate subnets with eight lncRNAs, 29 miRNAs, and 237 mRNAs were detected through clustering analyses, whereas GO enrichment analysis of identified RNAs revealed 510, 22, and 11 significantly enriched GO terms related to MAP infection in biological process, molecular function, and cellular component categories, respectively. The main metabolic-signaling pathways related to MAP infection that were enriched included the immune system process, defense response, response to cytokine, leukocyte migration, regulation of T cell activation, defense response to bacterium, NOD-like receptor, B cell receptor, TNF, NF-kappa B, IL-17, and T cell receptor signaling pathways. Contributions of transcriptome profiles from MAP-positive and MAP-negative sample groups plus a ceRNA regulatory network underlying phenotypic differences in the intensity of pathogenicity of JD provided novel insights into molecular mechanisms associated with immune system responses to MAP infection in dairy cattle.
副结核或约翰氏病（JD）是由副结核分枝杆菌亚种（MAP）引起的一种慢性肉芽肿性肠胃炎，在全球范围内给奶牛群造成了巨大的经济损失并降低了动物福利。目前，奶牛对MAP感染的免疫反应所涉及的分子机制和生物学功能尚不清楚。我们的目的是整合转录组图谱和竞争性内源RNA（ceRNA）网络分析，以鉴定参与奶牛MAP感染外周血单核细胞（PBMC）分子调控的关键信使RNA（mRNA）和调控RNA。通过整合基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，共鉴定出28个长链非编码RNA（lncRNA）、42个微小RNA（miRNA）和370个mRNA。在此方面，我们鉴定出21个参与MAP感染的枢纽基因（、、、、、、、、、、、、、、、、、、、、和）。此外，通过聚类分析检测到8个候选子网，包含8个lncRNA、29个miRNA和237个mRNA，而对鉴定出的RNA进行的GO富集分析分别在生物过程、分子功能和细胞组成类别中揭示了510个、22个和11个与MAP感染显著富集的GO术语。与MAP感染相关的主要代谢信号通路包括免疫系统过程、防御反应、对细胞因子的反应、白细胞迁移、T细胞活化调节、对细菌的防御反应、NOD样受体、B细胞受体、TNF、NF-κB、IL-17和T细胞受体信号通路。来自MAP阳性和MAP阴性样本组的转录组图谱以及JD致病性强度表型差异背后的ceRNA调控网络为奶牛对MAP感染的免疫系统反应相关分子机制提供了新的见解。
