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阻塞性睡眠呼吸暂停和鼾症与三叶因子家族肽3(TFF3)的下调有关——口腔黏液成分变化的影响

Obstructive sleep apnea and rhonchopathy are associated with downregulation of trefoil factor family peptide 3 (TFF3)-Implications of changes in oral mucus composition.

作者信息

Siber-Hoogeboom Regina, Schicht Martin, Hoogeboom Sebastian, Paulsen Friedrich, Traxdorf Maximilian

机构信息

Department of Anatomy II, Friedrich Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Department of Otorhinolaryngology, Head & Neck Surgery, Friedrich Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

出版信息

PLoS One. 2017 Oct 13;12(10):e0185200. doi: 10.1371/journal.pone.0185200. eCollection 2017.

Abstract

STUDY OBJECTIVES

Trefoil factor family (TFF) peptides belong to the family of mucin-associated peptides and are expressed in most mucosal surfaces. TFF peptides carry out functions such as proliferation and migration enhancement, anti-apoptosis, and wound healing. Moreover, TFFs are associated with mucins and interact with them as "linker peptides", thereby influencing mucus viscosity. To test the hypothesis that in rhonchopathy and obstructive sleep apnea (OSA) changes occur in the expression of TFF3 and -2 that could contribute to changes in mucus viscosity, leading to an increase in upper airway resistance during breathing.

METHODS

RT-PCR, Western-blot, immunohistochemistry and ELISA were performed to detect and quantify TFF3 and -2 in uvula samples. In addition, 99 saliva samples from patients with mild, moderate or severe OSA, as well as samples from rhonchopathy patients and from healthy volunteers, were analyzed by ELISA.

RESULTS

TFF3 was detected in all uvula samples. Immunohistochemistry revealed a subjectively decreasing antibody reactivity of the uvula epithelia with increasing disease severity. ELISA demonstrated significantly higher TFF3 saliva protein concentrations in the healthy control group compared to cases with rhonchopathy and OSA. Predisposing factors of OSA such as BMI or age showed no correlation with TFF3. No significant changes were observed with regard to TFF2.

CONCLUSIONS

The results suggest the involvement of TFF3 in the pathogenesis of rhonchopathy and OSA and lead to the hypothesis that reduction of TFF3 production by the epithelium and subepithelial mucous glands of the uvula contribute to an increase in breathing resistance due to a change in mucus organization.

摘要

研究目的

三叶因子家族(TFF)肽属于黏蛋白相关肽家族,在大多数黏膜表面表达。TFF肽具有促进增殖和迁移、抗凋亡及伤口愈合等功能。此外,TFF与黏蛋白相关,作为“连接肽”与它们相互作用,从而影响黏液黏度。为验证以下假说:在鼾症和阻塞性睡眠呼吸暂停(OSA)中,TFF3和-2的表达发生变化,这可能导致黏液黏度改变,进而导致呼吸时上气道阻力增加。

方法

采用逆转录聚合酶链反应(RT-PCR)、蛋白质免疫印迹法(Western-blot)、免疫组织化学和酶联免疫吸附测定(ELISA)检测并定量悬雍垂样本中的TFF3和-2。此外,采用ELISA分析了99份来自轻度、中度或重度OSA患者的唾液样本,以及鼾症患者和健康志愿者的样本。

结果

在所有悬雍垂样本中均检测到TFF3。免疫组织化学显示,随着疾病严重程度增加,悬雍垂上皮的抗体反应性主观上降低。ELISA显示,与鼾症和OSA患者相比,健康对照组的TFF3唾液蛋白浓度显著更高。OSA的易感因素如体重指数(BMI)或年龄与TFF3无相关性。未观察到TFF2有显著变化。

结论

结果提示TFF3参与了鼾症和OSA的发病机制,并得出以下假说:悬雍垂上皮和上皮下黏液腺产生的TFF3减少,由于黏液组织改变,导致呼吸阻力增加。

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