HDAC inhibitor sodium butyrate prevents allergic rhinitis and alters lncRNA and mRNA expression profiles in the nasal mucosa of mice
HDAC inhibitor sodium butyrate prevents allergic rhinitis and alters lncRNA and mRNA expression profiles in the nasal mucosa of mice
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HDAC 抑制剂丁酸钠可预防过敏性鼻炎并改变小鼠鼻粘膜中的 lncRNA 和 mRNA 表达谱
DOI：
10.3892/ijmm.2020.4489
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发表时间：
2020-04-01
影响因子：
5.4
通讯作者：
Chen, Fu-Quan
中科院分区：
文献类型：
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作者：
Wang, Jie;Cui, Mu;Chen, Fu-Quan
我们以前的研究表明，组蛋白去乙酰化酶抑制剂丁酸钠（NaB）鼻内给药对小鼠变应性鼻炎（AR）模型具有治疗作用。然而，NaB在口服和口服给药时是否对AR有效，以及其对基因表达的潜在影响仍然未知。本研究的目的是探讨预防效果的NaB对AR添加到新断奶的小鼠的饮食和评估的变化，在鼻粘膜中的长非编码（lnc）RNA和mRNA的表达谱。将小鼠随机分成如下三组：i）对照（C）组（未处理）; ii）AR组[用卵清蛋白（OVA）处理];和iii）NaB + AR组（用OVA和NaB处理）。NaB + AR组在饲料中给予NaB（30 g/kg饲料），而其他两组在3至6周龄之间喂食正常饲料。在7周龄时，开始施用OVA以在AR和NaB + AR组中诱导AR。模型建立后，进行行为学评估、蛋白质印迹和基因表达分析。NaB在小鼠AR模型中表现出预防作用，减少了组蛋白脱乙酰酶1（HDAC 1）和HDAC 8表达的增加，并增加了OVA诱导的组蛋白H3在赖氨酸9处的乙酰化。此外，NaB增加AR相关的白细胞介素2（IL-2）、干扰素γ和IL-17的低表达，降低IL-4、IL-5和转化生长因子β1的表达。基因本体和途径分析揭示了各组中的前10个途径。预测八聚体结合转录因子1、亲嗜性病毒整合位点1和配对盒4是lncRNA（NONMMUT 057309）的靶基因。因此，NaB可能对AR具有预防作用。此外，lncRNA和mRNA的表达谱在鼻粘膜与AR小鼠不同的NaB治疗后显着。这些结果可能为AR的发病机制提供见解，并提出新的治疗靶点。
Our previous study demonstrated that intranasal administration of histone deacetylase inhibitor sodium butyrate (NaB) exhibits therapeutic effects on a mouse model of allergic rhinitis (AR). However, whether NaB is effective on AR when administered orally and prophylactically, as well as its potential effects on gene expression, remained unknown. The present study aimed to investigate the preventive effect of NaB on AR when added to the diet of newly weaned mice and to evaluate the changes in long non-coding (lnc)RNA and mRNA expression profiles in the nasal mucosa. Mice were randomly divided into three groups as follows: i) Control (C) group, (no treatment); ii) AR group [treated with ovalbumin (OVA)]; and iii) NaB + AR group (treated with OVA and NaB). The NaB + AR group was administered NaB in their feed (30 g/kg chow), whereas the other two groups were fed normal feed between 3 and 6 weeks of age. At 7 weeks of age, OVA administration was initiated to induce AR in the AR and NaB + AR groups. Following model establishment, behavioral assessments, western blotting and gene expression analysis were performed. NaB exhibited a preventive effect in the murine AR model, diminished the increases in histone deacetylase 1 (HDAC1) and HDAC8 expression and increased OVA-induced acetylation of histone H3 at lysine 9. In addition, NaB increased the AR-associated low expression of interleukin 2 (IL-2), interferon γ and IL-17 and decreased the expression of IL-4, IL-5 and transforming growth factor β1. Gene Ontology and pathway analyses revealed the top 10 pathways among the groups. Octamer-binding transcription factor 1, ecotropic viral integration site 1 and paired box 4 were predicted to be target genes of lncRNA (NONMMUT057309). Thus, NaB may exhibit a preventive effect on AR. Additionally, the lncRNA and mRNA expression profiles in the nasal mucosa of mice with AR differed significantly following NaB treatment. These results may provide insights into the pathogenesis of AR and suggest new treatment targets.