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Expression of ACE2 and TMPRSS2 proteins in the upper and lower aerodigestive tracts of rats
bioRxiv - Pathology Pub Date : 2020-05-15 , DOI: 10.1101/2020.05.14.097204
Taku Sato , Rumi Ueha , Takao Goto , Akihito Yamauchi , Kenji Kondo , Tatsuya Yamasoba

Objective: Patients with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit not only respiratory symptoms but also symptoms of chemo-sensitive disorders and kidney failure. Cellular entry of SARS-CoV-2 depends on the binding of its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike protein-priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 are considered to enhance the invading capacity of SARS-CoV-2. Methods: To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, lung, and kidney of rats through immunohistochemistry. Results: Strong co-expression of ACE2 and TMPRSS2 proteins was observed in the nasal respiratory epithelium, trachea, bronchioles, alveoli, kidney, and taste buds of the tongue. Remarkably, TMPRSS2 expression was much stronger in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID-19, such as the loss of taste, loss of olfaction, respiratory dysfunction, and acute nephropathy. Conclusions: A wide range of organs have been speculated to be affected by SARS-CoV-2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID-19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID-19.

中文翻译:

ACE2和TMPRSS2蛋白在大鼠上消化道和下消化道中的表达

目的:由严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)引起的冠状病毒病2019(COVID-19)患者不仅表现出呼吸道症状,而且表现出化学敏感性疾病和肾衰竭的症状。SARS-CoV-2的细胞进入取决于其刺突蛋白与称为血管紧张素转化酶2(ACE2)的细胞受体的结合,以及随后宿主细胞蛋白酶(包括跨膜蛋白酶丝氨酸2(TMPRSS2))引发的刺突蛋白引发。因此,ACE2和TMPRSS2的高表达被认为可以增强SARS-CoV-2的入侵能力。方法:为了阐明由SARS-CoV-2引起的航空消化系统疾病的潜在组织学机制,我们调查了ACE2和TMPRSS2蛋白在舌部,部分pa鼻硬组织的消化道中的表达,通过免疫组织化学法观察大鼠的喉与下咽,气管,食道,肺和肾脏。结果:在鼻呼吸道上皮,气管,细支气管,肺泡,肾脏和舌头的味蕾中观察到了ACE2和TMPRSS2蛋白的强共表达。值得注意的是,TMPRSS2在外周肺泡中的表达要强于中央肺泡。这些结果与报道的COVID-19的临床症状相吻合,例如味觉丧失,嗅觉丧失,呼吸功能障碍和急性肾病。结论:根据ACE2和TMPRSS2的表达水平,已推测广泛的器官受到SARS-CoV-2的影响。肺中TMPRSS2的差异分布表明,TMPRSS2表达可能会加剧COVID-19症状。
更新日期:2020-05-15
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