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二肽基肽酶 4(DPP4)是中东呼吸综合征冠状病毒受体,在吸烟者和慢性阻塞性肺疾病患者的肺部中上调。

DPP4, the Middle East Respiratory Syndrome Coronavirus Receptor, is Upregulated in Lungs of Smokers and Chronic Obstructive Pulmonary Disease Patients.

机构信息

Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University HospitalGhent, Belgium.

Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.

出版信息

Clin Infect Dis. 2018 Jan 6;66(1):45-53. doi: 10.1093/cid/cix741.

Abstract

BACKGROUND

Middle East respiratory syndrome coronavirus (MERS-CoV) causes pneumonia with a relatively high case fatality rate in humans. Smokers and chronic obstructive pulmonary disease (COPD) patients have been reported to be more susceptible to MERS-CoV infection. Here, we determined the expression of MERS-CoV receptor, dipeptidyl peptidase IV (DPP4), in lung tissues of smokers without airflow limitation and COPD patients in comparison to nonsmoking individuals (never-smokers).

METHODS

DPP4 expression was measured in lung tissue of lung resection specimens of never-smokers, smokers without airflow limitation, COPD GOLD stage II patients and in lung explants of end-stage COPD patients. Both control subjects and COPD patients were well phenotyped and age-matched. The mRNA expression was determined using qRT-PCR and protein expression was quantified using immunohistochemistry.

RESULTS

In smokers and subjects with COPD, both DPP4 mRNA and protein expression were significantly higher compared to never-smokers. Additionally, we found that both DPP4 mRNA and protein expression were inversely correlated with lung function and diffusing capacity parameters.

CONCLUSIONS

We provide evidence that DPP4 is upregulated in the lungs of smokers and COPD patients, which could partially explain why these individuals are more susceptible to MERS-CoV infection. These data also highlight a possible role of DPP4 in COPD pathogenesis.

摘要

背景

中东呼吸综合征冠状病毒(MERS-CoV)可引起肺炎,人类感染该病毒的病死率相对较高。有报道称,吸烟者和慢性阻塞性肺疾病(COPD)患者更容易感染 MERS-CoV。在此,我们测定了无气流受限的吸烟者和 COPD 患者的肺组织中 MERS-CoV 受体二肽基肽酶 4(DPP4)的表达水平,并与不吸烟者(从不吸烟者)进行了比较。

方法

我们测量了肺切除术标本中从不吸烟者、无气流受限的吸烟者、COPD GOLD Ⅱ期患者以及终末期 COPD 患者肺组织中的 DPP4 表达。所有对照者和 COPD 患者均进行了良好的表型分析和年龄匹配。使用 qRT-PCR 测定 mRNA 表达,使用免疫组织化学定量蛋白质表达。

结果

与从不吸烟者相比,吸烟者和 COPD 患者的 DPP4 mRNA 和蛋白表达均显著升高。此外,我们发现 DPP4 mRNA 和蛋白表达均与肺功能和弥散量参数呈负相关。

结论

我们提供的证据表明,DPP4 在吸烟者和 COPD 患者的肺部上调,这部分解释了为什么这些人更容易感染 MERS-CoV。这些数据还突出了 DPP4 在 COPD 发病机制中的可能作用。

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