Zheng Zheng, Ge Yinlin, Zhang Jinyu, Xue Meilan, Li Quan, Lin Dongliang, Ma Wenhui
Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China.
Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266021, P.R. China.
Mol Med Rep. 2015 Jun;11(6):4149-57. doi: 10.3892/mmr.2015.3318. Epub 2015 Feb 9.
Omega‑3 and ‑6 polyunsaturated fatty acids (PUFAs) can directly or indirectly regulate immune homeostasis via inflammatory pathways, and components of these pathways are crucial targets of microRNAs (miRNAs). However, no study has examined the changes in the miRNA transcriptome during PUFA‑regulated inflammatory processes. Here, we established PUFA diet‑induced autoimmune‑prone (AP) and autoimmune‑averse (AA) rat models, and studied their physical characteristics and immune status. Additionally, miRNA expression patterns in the rat models were compared using microarray assays and bioinformatic methods. A total of 54 miRNAs were differentially expressed in common between the AP and the AA rats, and the changes in rno‑miR‑19b‑3p, ‑146b‑5p and ‑183‑5p expression were validated using stem‑loop reverse transcription‑quantitative polymerase chain reaction. To better understand the mechanisms underlying PUFA‑regulated miRNA changes during inflammation, computational algorithms and biological databases were used to identify the target genes of the three validated miRNAs. Furthermore, Gene Ontology (GO) term annotation and KEGG pathway analyses of the miRNA targets further allowed to explore the potential implication of the miRNAs in inflammatory pathways. The predicted PUFA‑regulated inflammatory pathways included the Toll‑like receptor (TLR), T cell receptor (TCR), NOD‑like receptor (NLR), RIG‑I‑like receptor (RLR), mitogen‑activated protein kinase (MAPK) and the transforming growth factor‑β (TGF‑β) pathway. This study is the first report, to the best of our knowledge, on in vivo comparative profiling of miRNA transcriptomes in PUFA diet‑induced inflammatory rat models using a microarray approach. The results provide a useful resource for future investigation of the role of PUFA‑regulated miRNAs in immune homeostasis.
ω-3和ω-6多不饱和脂肪酸(PUFAs)可通过炎症途径直接或间接调节免疫稳态,而这些途径的组成部分是微小RNA(miRNAs)的关键作用靶点。然而,尚无研究探讨PUFAs调节炎症过程中miRNA转录组的变化。在此,我们建立了PUFA饮食诱导的自身免疫易感(AP)和自身免疫抵抗(AA)大鼠模型,并研究了它们的身体特征和免疫状态。此外,利用微阵列分析和生物信息学方法比较了大鼠模型中的miRNA表达模式。AP和AA大鼠共有54种miRNA差异表达,通过茎环逆转录定量聚合酶链反应验证了rno-miR-19b-3p、-146b-5p和-183-5p表达的变化。为了更好地理解炎症过程中PUFAs调节miRNA变化的潜在机制,我们使用计算算法和生物学数据库来识别这三种经验证的miRNA的靶基因。此外,对miRNA靶标的基因本体(GO)术语注释和KEGG通路分析进一步有助于探索miRNA在炎症通路中的潜在作用。预测的PUFAs调节的炎症通路包括Toll样受体(TLR)、T细胞受体(TCR)、NOD样受体(NLR)、RIG-I样受体(RLR)、丝裂原活化蛋白激酶(MAPK)和转化生长因子-β(TGF-β)通路。据我们所知,本研究是首次使用微阵列方法对PUFA饮食诱导的炎症大鼠模型中的miRNA转录组进行体内比较分析。这些结果为未来研究PUFAs调节的miRNAs在免疫稳态中的作用提供了有用的资源。