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ACE2 对 SARS-CoV-2 感染肾细胞的重要性。

Importance of ACE2 for SARS-CoV-2 Infection of Kidney Cells.

机构信息

Medizinische Klinik D, Universitätsklinikum Münster, 48149 Münster, Germany.

Research Group Regulatory Mechanisms of Inflammation, Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Münster, 48149 Münster, Germany.

出版信息

Biomolecules. 2023 Mar 3;13(3):472. doi: 10.3390/biom13030472.

Abstract

In late 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the causative agent of coronavirus disease 2019 (COVID-19) emerged in China and spread rapidly around the world, causing an ongoing pandemic of global concern. COVID-19 proceeds with moderate symptoms in most patients, whereas others experience serious respiratory illness that requires intensive care treatment and may end in death. The severity of COVID-19 is linked to several risk factors including male sex, comorbidities, and advanced age. Apart from respiratory complications, further impairments by COVID-19 affecting other tissues of the human body are observed. In this respect, the human kidney is one of the most frequently affected extrapulmonary organs and acute kidney injury (AKI) is known as a direct or indirect complication of SARS-CoV-2 infection. The aim of this work was to investigate the importance of the protein angiotensin-converting enzyme 2 (ACE2) for a possible cell entry of SARS-CoV-2 into human kidney cells. First, the expression of the cellular receptor ACE2 was demonstrated to be decisive for viral SARS-CoV-2 cell entry in human AB8 podocytes, whereas the presence of the transmembrane protease serine 2 (TMPRSS2) was dispensable. Moreover, the ACE2 protein amount was well detectable by mass spectrometry analysis in human kidneys, while TMPRSS2 could be detected only in a few samples. Additionally, a negative correlation of the ACE2 protein abundance to male sex and elderly aged females in human kidney tissues was demonstrated in this work. Last, the possibility of a direct infection of kidney tubular renal structures by SARS-CoV-2 was demonstrated.

摘要

2019 年末,新型严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)作为 2019 年冠状病毒病(COVID-19)的病原体在中国出现,并迅速在全球传播,引发了全球关注的持续大流行。COVID-19 在大多数患者中表现为中度症状,而其他患者则患有严重的呼吸道疾病,需要重症监护治疗,并且可能导致死亡。COVID-19 的严重程度与包括男性、合并症和高龄在内的几个危险因素有关。除了呼吸道并发症外,COVID-19 还会对人体的其他组织造成进一步的损害。在这方面,人类肾脏是最常受影响的肺外器官之一,急性肾损伤(AKI)被认为是 SARS-CoV-2 感染的直接或间接并发症。本研究旨在探讨血管紧张素转换酶 2(ACE2)蛋白对 SARS-CoV-2 进入人肾细胞的重要性。首先,证明细胞受体 ACE2 的表达对 SARS-CoV-2 在人 AB8 足细胞中的病毒细胞进入至关重要,而跨膜蛋白酶丝氨酸 2(TMPRSS2)的存在则是可有可无的。此外,通过质谱分析在人肾脏中很好地检测到 ACE2 蛋白的含量,而 TMPRSS2 只能在少数样本中检测到。此外,本研究还证明了 ACE2 蛋白丰度与人肾脏组织中男性和老年女性的相关性呈负相关。最后,证明了 SARS-CoV-2 直接感染肾小管肾结构的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ca/10046276/e966d3e0c83a/biomolecules-13-00472-g001.jpg

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