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

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Effects of increasing sensitizing doses of ovalbumin on airway hyperresponsiveness in asthmatic mice

“…The sensitizing doses utilized in current murine studies typically range from 10 to 100 μg 7,17–19 . However, the effects of various doses within this range have not been thoroughly investigated.…”

“…The sensitizing doses utilized in current murine studies typically range from 10 to 100 μg. 7 , 17 , 18 , 19 However, the effects of various doses within this range have not been thoroughly investigated. In 1999, Sakai et al 20 demonstrated the impact of sensitive OVA doses (0, 10, 100, and 1000 μg) on AHR; their study suggested that sensitization with a dose of 10 μg may be more effective than with a dose of 100 μg but almost completely inhibited at a dose of 1000 μg.…”

“…6 However, despite being described as the "classical" murine allergic asthma model, there is no standardized OVA model due to variations in sensitization and challenge methods, OVA doses, use of alum, number of challenges, and protocol duration across studies. [7][8][9][10] The previous study has demonstrated that intraperitoneal injection of OVA and alum once a week for 2 weeks is the most straightforward and effective approach to induce an asthmatic reaction in mice. 11 However, the inconsistent use of sensitizing OVA doses in current studies [12][13][14] and the lack of research on their effect on AHR necessitate further investigation.…”

“…OVA is the most commonly utilized allergen for the induction of asthma in mouse models 6 . However, despite being described as the “classical” murine allergic asthma model, there is no standardized OVA model due to variations in sensitization and challenge methods, OVA doses, use of alum, number of challenges, and protocol duration across studies 7–10 …”