Gene expression profiles and bioinformatics analysis in lung samples from ovalbumin-induced asthmatic mice.

Gene expression profiles and bioinformatics analysis in lung samples from ovalbumin-induced asthmatic mice.
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来自卵巢蛋白诱导的哮喘小鼠的肺样品中的基因表达谱和生物信息学分析。

DOI:
10.1186/s12890-023-02306-w
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发表时间:
2023-02-02
影响因子:
3.1
通讯作者:
Yan, Guanghai
Yan, Guanghai
中科院分区:
医学3区
文献类型:
--
作者:
Song, Yilan;Jiang, Jingzhi;Bai, Qiaoyun;Liu, Siqi;Zhang, Yalin;Xu, Chang;Piao, Hongmei;Li, Liangchang;Yan, Guanghai

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哮喘的特征是慢性炎症和呼吸道重塑。然而,对卵白蛋白(OVA)诱导的小鼠哮喘的基因表达谱的研究却很有限。在这里,我们利用基因芯片和生物信息学分析,探索了OVA诱导的哮喘小鼠肺组织中的基因表达谱。为建立OVA诱导的小鼠哮喘模型,分别于第0、7、14天给予OVA腹腔致敏,然后雾化吸入OVA,每周3次,共8周。收集肺组织,进行基因芯片分析、生物信息学分析和表达验证。肺组织芯片数据显示,正常小鼠和哮喘小鼠肺组织差异表达基因分别为3754个和2976个,其中上调表达1647个,下调2106个,上调1201个,下调1766个。GO分析表明,上调的基因在炎症反应、参与炎症反应的白细胞迁移和Notch信号通路中都有丰富的表达。KEGG通路分析表明,上调基因的丰富通路项包括Toll样受体信号通路和Th17细胞分化信号通路。此外,根据已发表的有关哮喘和炎症的文献,我们筛选出下调的基因如Smg7、Sumo2和Stat5a,上调的基因如Myl9、Fos和TLR4。根据mRNA-lncRNA共表达网络,我们筛选了与上述基因相关的lncRNAs,包括NONMMUT032848、NONMMUT008873、NONMMUT009478和NONMMUT006807,以及NONMMUT052633、NONMMUT05340和NONMMUT042325。用实时定量聚合酶链式反应和免疫印迹方法验证上述基因在肺组织中的表达变化。总体而言,我们对OVA诱导的哮喘小鼠的肺样本进行了基因芯片,并总结了核心mRNAs及其相关的lncRNAs。本研究为进一步研究哮喘的治疗靶点提供了依据。网上版载有补充材料,可在10.1186/s12890-023-023-w查阅。
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. The online version contains supplementary material available at 10.1186/s12890-023-02306-w.
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