4. ACE2 is expressed in various organs and plays an important role in organ injury secondary to COVID-19
According to the latest clinical research, the infected patients not only have respiratory symptoms, but also have cardiovascular, digestive, central system, renal and other symptoms(Guan et al. , 2020). ACE2 is a type Ⅰ integral membrane glycoprotein widely expressed in lung, heart, endothelium, kidneys, gastrointestinal tract and so on(Zouet al. , 2020). Based on the findings, the organs, which highly express ACE2, may be vulnerable to SARS-CoV-2 infection. The decrease of ACE2 expression may accelerate lung injury because ACE2 is a protective molecule of RAAS, which induce the inflammatory response and organ damage. Binding to the ACE2 receptor is a critical initial step for SARS-CoV-2 to entry into target cells. In the process of infection, it is likely to require two kinds of transmembrane proteases: ADAM17 metalloproteinase and TMPRSS2 transmembrane protease. ACE2 could be cut by ADAM17 metalloproteinase, which hinders the binding of virus and ACE2(Lambert et al. , 2005); while TMPRSS2 transmembrane protease is required to the process, assisting the combination of ACE2 and SARS-CoV-2(Iwata-Yoshikawa et al. , 2019). SARS-CoV-2 appears not only to gain the initial entry through ACE2 but also subsequently to down-regulate ACE2 expression, which leads to the immune response imbalance caused by ACE/Ang Ⅱ/AT1R activation(Vaduganathan et al. , 2020). The down-regulation of ACE2 reduces the level of Ang (1-7), and subsequently increases the production of Ang Ⅱ, which activates the RAAS and enhances inflammation. (Figure 2 )