Jilin Key Laboratory for Immune and Targeting Research On Common Allergic Diseases, Yanbian University, Yanji, 133002, People's Republic of China.
Department of Anatomy, Histology and Embryology, Yanbian University Medical College, No. 977, Gongyuan Road, Yanji, 133002, Jilin Province, People's Republic of China.
BMC Pulm Med. 2023 Feb 2;23(1):50. doi: 10.1186/s12890-023-02306-w.
Asthma is characterized by chronic inflammation and airway remodeling. However, limited study is conducted on the gene expression profiles of ovalbumin (OVA) induced asthma in mice. Here, we explored the gene expression profiles in lung tissues from mice with OVA-induced asthma using microarray and bioinformatics analysis.
For establishment of OVA-induced asthma model, mice first received intraperitoneal sensitization with OVA on day 0, 7 and 14, followed by atomizing inhalation of OVA 3 times a week for 8 weeks. The lung tissues were collected and subjected to microarray analysis, bioinformatics analysis and expression validation.
Microarray data of lung tissues suggested that 3754 lncRNAs and 2976 mRNAs were differentially expressed in lung tissues between control and asthmatic mice, including 1647 up-regulated and 2106 down-regulated lncRNAs, and 1201 up-regulated and 1766 down-regulated mRNAs. GO analysis displayed that the up-regulated genes were enriched in inflammatory response, leukocyte migration involved in inflammatory response, and Notch signaling pathway. KEGG pathway analysis indicated that the enriched pathway terms of the up-regulated gene included Toll-like receptor signaling pathway and Th17 cell differentiation signaling pathway. Additionally, based on the previously published literatures on asthma and inflammation, we screened out down-regulated genes, such as Smg7, Sumo2, and Stat5a, and up-regulated genes, such as Myl9, Fos and Tlr4. According to the mRNA-lncRNA co-expression network, we selected lncRNAs associated with above genes, including the down-regulated lncRNAs of NONMMUT032848, NONMMUT008873, NONMMUT009478, and NONMMUT006807, and the up-regulated lncRNAs of NONMMUT052633, NONMMUT05340 and NONMMUT042325. The expression changes of the above genes were validated in lung tissues by real-time quantitaive PCR and Western blot.
Overall, we performed gene microarray on lung samples from OVA-induced asthmatic mice and summarized core mRNAs and their related lncRNAs. This study may provide evidence for further research on the therapeutic targets of asthma.
哮喘的特征是慢性炎症和气道重塑。然而，关于卵清蛋白（OVA）诱导的哮喘小鼠的基因表达谱的研究有限。在这里，我们使用微阵列和生物信息学分析来研究 OVA 诱导的哮喘小鼠肺组织中的基因表达谱。
为了建立 OVA 诱导的哮喘模型，首先在第 0、7 和 14 天对小鼠进行腹腔内致敏，然后每周雾化吸入 OVA 3 次，共 8 周。收集肺组织进行微阵列分析、生物信息学分析和表达验证。
肺组织微阵列数据显示，对照组和哮喘组小鼠肺组织中差异表达的 lncRNA 有 3754 个，mRNA 有 2976 个，其中上调的 lncRNA 有 1647 个，下调的 lncRNA 有 2106 个；上调的 mRNA 有 1201 个，下调的 mRNA 有 1766 个。GO 分析显示，上调基因富集于炎症反应、白细胞迁移参与炎症反应和 Notch 信号通路。KEGG 通路分析表明，上调基因富集的通路术语包括 Toll 样受体信号通路和 Th17 细胞分化信号通路。此外，基于先前发表的哮喘和炎症文献，我们筛选出下调基因，如 Smg7、Sumo2 和 Stat5a，以及上调基因，如 Myl9、Fos 和 Tlr4。根据 mRNA-lncRNA 共表达网络，我们选择与上述基因相关的 lncRNA，包括下调的 lncRNA NONMMUT032848、NONMMUT008873、NONMMUT009478 和 NONMMUT006807，以及上调的 lncRNA NONMMUT052633、NONMMUT05340 和 NONMMUT042325。通过实时定量 PCR 和 Western blot 验证了上述基因在肺组织中的表达变化。
总的来说，我们对 OVA 诱导的哮喘小鼠的肺样本进行了基因微阵列分析，并总结了核心 mRNA 及其相关 lncRNA。本研究可为哮喘治疗靶点的进一步研究提供依据。
