Importance of ACE2 for SARS-CoV-2 Infection of Kidney Cells.
Marie-Kristin KrollSebastian SchloerPeynaz CandanNadia KorthalsChristoph WenzelHannah IhleKevin GilhausKim Rouven LiedtkeMichael SchöfbänkerBeate SurmannRita SchröterUte NeugebauerGita MallStefan OswaldStephan LudwigUrsula RescherBeate VollenbrökerGiuliano CiarimboliPublished in: Biomolecules (2023)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- coronavirus disease
- endothelial cells
- angiotensin converting enzyme
- acute kidney injury
- angiotensin ii
- induced pluripotent stem cells
- mass spectrometry
- pluripotent stem cells
- risk factors
- gene expression
- high glucose
- stem cells
- newly diagnosed
- end stage renal disease
- chronic kidney disease
- ejection fraction
- cell therapy
- cardiac surgery
- prognostic factors
- cell death
- depressive symptoms
- physical activity
- cell cycle arrest
- signaling pathway
- community dwelling
- middle aged
- mesenchymal stem cells
- amino acid
- protein protein