Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Department of Biology, Lund University, Lund, Sweden.
Mayo Clin Proc. 2020 Sep;95(9):1989-1999. doi: 10.1016/j.mayocp.2020.06.018. Epub 2020 Jul 19.
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has rapidly caused a global pandemic associated with a novel respiratory infection: coronavirus disease-19 (COVID-19). Angiotensin-converting enzyme-2 (ACE2) is necessary to facilitate SARS-CoV-2 infection, but-owing to its essential metabolic roles-it may be difficult to target it in therapies. Transmembrane protease serine 2 (TMPRSS2), which interacts with ACE2, may be a better candidate for targeted therapies. Using publicly available expression data, we show that both ACE2 and TMPRSS2 are expressed in many host tissues, including lung. The highest expression of ACE2 is found in the testes, whereas the prostate displays the highest expression of TMPRSS2. Given the increased severity of disease among older men with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in severity of disease. We show that expression levels of ACE2 and TMPRSS2 are overall comparable between men and women in multiple tissues, suggesting that differences in the expression levels of TMPRSS2 and ACE2 in the lung and other non-sex-specific tissues may not explain the gender disparities in severity of SARS CoV-2. However, given their instrumental roles for SARS-CoV-2 infection and their pleiotropic expression, targeting the activity and expression levels of TMPRSS2 is a rational approach to treat COVID-19.
严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）迅速引发了一场全球性大流行，与新型呼吸道感染有关：冠状病毒病 19（COVID-19）。血管紧张素转化酶 2（ACE2）是促进 SARS-CoV-2 感染所必需的，但由于其重要的代谢作用，在治疗中靶向它可能很困难。与 ACE2 相互作用的跨膜丝氨酸蛋白酶 2（TMPRSS2）可能是靶向治疗的更好候选者。利用公开的表达数据，我们表明 ACE2 和 TMPRSS2 均在许多宿主组织中表达，包括肺。ACE2 的最高表达在睾丸中发现，而前列腺显示 TMPRSS2 的最高表达。鉴于 SARS-CoV-2 感染中老年男性疾病的严重程度增加，我们探讨了 ACE2 和 TMPRSS2 在其对疾病严重程度性别差异的贡献中的潜在作用。我们表明，ACE2 和 TMPRSS2 的表达水平在多个组织中总体上在男性和女性之间相当，这表明肺和其他非性别特异性组织中 TMPRSS2 和 ACE2 的表达水平差异不能解释 SARS-CoV-2 严重程度的性别差异。然而，鉴于它们在 SARS-CoV-2 感染中的重要作用及其多效性表达，靶向 TMPRSS2 的活性和表达水平是治疗 COVID-19 的合理方法。
