Intermittent hypoxia induces turbinate mucosal hypertrophy via upregulating the gene expression related to inflammation and EMT in rats
Intermittent hypoxia induces turbinate mucosal hypertrophy via upregulating the gene expression related to inflammation and EMT in rats
复制标题
DOI：
10.1007/s11325-020-02162-6
复制
发表时间：
2020-08-06
影响因子：
2.5
通讯作者：
Ono, Takashi
中科院分区：
文献类型：
--
作者：
Kuma, Yo-ichiro;Hosomichi, Jun;Ono, Takashi
目的慢性间歇性缺氧（IH）在阻塞性睡眠呼吸暂停（OSA）的发生发展中起着重要作用。在啮齿类动物模型中，IH损害鼻上颌复合体的生长以减小鼻气道腔的尺寸。尽管伴有炎症性粘膜肥大的鼻甲功能障碍与OSA有关，但IH在伴有炎症驱动的纤维化的鼻甲肥大中的作用尚不清楚。在此，我们的目的是阐明炎症性粘膜肥大和上皮间质转化（EMT）在下鼻甲IH的发病机制。方法7周龄雄性SD大鼠以20次/h的速率暴露于IH（4%O2 ~ 21%O2 + 0%CO2）中。结果术后3周，实验组鼻甲骨黏膜明显增厚，与对照组比较差异有统计学意义。免疫组化结果显示，IH可增加鼻甲黏膜中TGF β和N-cadherin的表达，降低E-cadherin的表达。定量PCR分析表明，IH不仅增强了炎症标志物Tnf-a、IL-1b和Nos 2的表达，而且增强了EMT标志物Tgf-b1、Col 1a 1和Postn的表达。结论IH通过上调鼻粘膜炎症和EMT相关基因表达诱导下鼻甲肥大。
Purpose Chronic intermittent hypoxia (IH) plays a pivotal role in the consequences of obstructive sleep apnea (OSA). It has been demonstrated that IH impairs nasomaxillary complex growth to reduce nasal airway cavity size in rodent models. Although turbinate dysfunction with inflammatory mucosal hypertrophy is related to OSA, the role of IH in turbinate hypertrophy with inflammation-driven fibrosis is unknown. Here, we aimed to clarify the pathogenesis of inflammatory mucosal hypertrophy and epithelial-mesenchymal transition (EMT) in the nasal turbinate under IH. Methods Seven-week-old male Sprague-Dawley rats were exposed to IH (4% O(2)to 21% O(2)with 0% CO2) at a rate of 20 cycles/h. Results Hypertrophy of the turbinate mucosa occurred after 3 weeks, with the turbinate mucosa of the experimental group becoming significantly thicker than in the control group. Immunostaining showed that IH increased the expression of TGF beta and N-cadherin and decreased E-cadherin expression in the turbinate mucosa. Quantitative PCR analysis demonstrated that IH enhanced the expression of not only the inflammatory markersTnf-a,Il-1b, andNos2but also the EMT markersTgf-b1,Col1a1, andPostn. Conclusions Collectively, these results suggest that IH induced turbinate hypertrophy via upregulation of gene expression related to inflammation and EMT in the nasal mucosa.