ACE2 and TMPRSS2 in human kidney tissue and urine extracellular vesicles with age, sex, and COVID-19.

IF 2.9 4区医学 Q2 PHYSIOLOGY Pflugers Archiv : European journal of physiology Pub Date : 2024-10-09 DOI:10.1007/s00424-024-03022-y

Marie Lykke Bach, Sara Laftih, Jesper K Andresen, Rune M Pedersen, Thomas Emil Andersen, Lone W Madsen, Kirsten Madsen, Gitte R Hinrichs, Rikke Zachar, Per Svenningsen, Lars Lund, Isik S Johansen, Lennart Friis Hansen, Yaseelan Palarasah, Boye L Jensen

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Abstract

SARS-CoV-2 virus infects cells by engaging with ACE2 requiring protease TMPRSS2. ACE2 is highly expressed in kidneys. Predictors for severe disease are high age and male sex. We hypothesized that ACE2 and TMPRSS2 proteins are more abundant (1) in males and with increasing age in kidney and (2) in urine and extracellular vesicles (EVs) from male patients with COVID-19 and (3) SARS-CoV-2 is present in urine and EVs during infection. Kidney cortex samples from patients subjected to cancer nephrectomy (male/female; < 50 years/˃75 years, n = 24; ˃80 years, n = 15) were analyzed for ACE2 and TMPRSS2 protein levels. Urine from patients hospitalized with SARS-CoV-2 infection was analyzed for ACE2 and TMPRSS2. uEVs were used for immunoblotting and SARS-CoV-2 mRNA and antigen detection. Tissue ACE2 and TMPRSS2 protein levels did not change with age. ACE2 was not more abundant in male kidneys in any age group. ACE2 protein was associated with proximal tubule apical membranes in cortex. TMPRSS2 was observed predominantly in the medulla. ACE2 was elevated significantly in uEVs and urine from patients with COVID-19 with no sex difference compared with urine from controls w/wo albuminuria. TMPRSS2 was elevated in uEVs from males compared to female. ACE2 and TMPRSS2 did not co-localize in uEVs/apical membranes. SARS-CoV-2 nucleoprotein and mRNA were not detected in urine. Higher kidney ACE2 protein abundance is unlikely to explain higher susceptibility to SARS-CoV-2 infection in males. Kidney tubular cells appear not highly susceptible to SARS-CoV-2 infection. Loss of ACE2 into urine in COVID could impact susceptibility and angiotensin metabolism.

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人体肾组织和尿液细胞外囊泡中的 ACE2 和 TMPRSS2 与年龄、性别和 COVID-19 的关系。

SARS-CoV-2 病毒通过与需要蛋白酶 TMPRSS2 的 ACE2 结合来感染细胞。ACE2 在肾脏中高度表达。预测严重疾病的因素是高龄和男性。我们假设：(1) 在男性肾脏中，随着年龄的增长，ACE2 和 TMPRSS2 蛋白的含量更高；(2) 在 COVID-19 男性患者的尿液和细胞外囊泡 (EV) 中，ACE2 和 TMPRSS2 蛋白的含量更高；(3) 在感染期间，SARS-CoV-2 存在于尿液和 EV 中。癌症肾切除术患者（男/女）的肾皮质样本；

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来源期刊

Pflugers Archiv : European journal of physiology 医学-生理学

CiteScore

8.80

自引率

2.20%

发文量

121

审稿时长

4-8 weeks

期刊介绍： Pflügers Archiv European Journal of Physiology publishes those results of original research that are seen as advancing the physiological sciences, especially those providing mechanistic insights into physiological functions at the molecular and cellular level, and clearly conveying a physiological message. Submissions are encouraged that deal with the evaluation of molecular and cellular mechanisms of disease, ideally resulting in translational research. Purely descriptive papers covering applied physiology or clinical papers will be excluded. Papers on methodological topics will be considered if they contribute to the development of novel tools for further investigation of (patho)physiological mechanisms.