A novel coronavirus (SARS-CoV-2) that broke out at the end of 2019 is a newly discovered highly pathogenic human coronavirus and has some similarities with severe acute respiratory syndrome coronavirus (SARS-CoV). Angiotensin-converting enzyme 2 (ACE2) is the receptor for infected cells by SARS-CoV. SARS-CoV can invade cells by binding to ACE2 through the spike protein and SARS-CoV-2 may also infect cells through ACE2. Meanwhile, ACE2 also plays an important role in the course of pneumonia. Therefore the possible role of ACE2 in SARS and coronavirus disease 2019 (COVID-19) is worth discussing. This paper briefly summarized the role of ACE2 in SARS, and discussed the possible function of ACE2 in COVID-19 and potential risk of infection with other organs. At last, the function of ACE2 was explored for possible treatment strategies for SARS. It is hoped to provide ideas and theoretical support for clinical treatment of COVID-19.
Vaccines and antibodies are currently effective intervention strategies for preventing and treating COVID-19. Angiotensin-converting enzyme 2 (ACE2), a primary binding receptor for SARS-CoV-2, is a potential target for the prevention and treatment of COVID-19. At present, therapeutics based on the strategies that block the binding of SARS-CoV-2 Spike protein to the ACE2 receptor have entered clinical trials. On December 5, 2022, the journal Nature published the results of a pharmacological intervention to downregulate ACE2 expression for prevention of SARS-CoV-2 infections. The study found that a nuclear receptor, farnesoid X receptor for bile acids, regulated ACE2 expression. The clinical drug ursodeoxycholic acid that was used to treat liver diseases could downregulate ACE2 expression and prevent SARS-CoV-2 infections, showing a new potential pathway in managing COVID-19.
Objective To investigate the expression of dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme 2 (ACE2) in lung tissues of patients with four different diseases including coronavirus disease 2019 (COVID-19), chronic obstructive pulmonary disease (COPD), pulmonary sarcoidosis and pulmonary bullae, and to find out the potential risk factors affecting COVID-19. Methods This study retrospectively analyzed the clinical data of 40 patients admitted to Renmin Hospital of Wuhan University with COVID-19 (COVID-19 group), COPD (COPD group), pulmonary sarcoidosis (pulmonary sarcoidosis group) and pulmonary bullae (pulmonary bullae group) and surgically resected paraffin-embedded pathological lung tissues were obtained from their lung tissue pathological specimens after surgery and paraffin embedding. The GEO database (https://www.ncbi.nlm.nih.gov/geo/) was used for bioinformatics analysis to explore the expression difference of DPP4 and ACE2 mRNA in COVID-19, COPD, pulmonary sarcoidosis and normal lung tissues. Immunohistochemistry method was used to detect the expression of DPP4 and ACE2 protein in lung tissues of each group and the average optical density was measured by image analysis software. Results The results of GEO database analysis showed that compared with pulmonary bullae group, the expression level of DPP4 mRNA had no significant difference in the COPD group and pulmonary sarcoidosis group (both P>0.05), but it was increased in the COVID-19 group (P<0.05); There was no significant difference in the expression level of ACE mRNA in the pulmonary sarcoidosis group (P>0.05), but it was increased in the lung tissue of COVID-19 group and COPD group (both P<0.05). The results of immunohistochemistry showed that DPP4 and ACE2 proteins were lowly expressed in the pulmonary sarcoidosis group and pulmonary bullae group, while their expression level was high in COVID-19 and COPD groups without significant difference (P>0.05). The expression of DPP4 and ACE2 proteins in COVID-19 group was not related to the patient’s gender and age (P>0.05), but was related to smoking and long smoking duration (P<0.05), and there was a positive correlation between DPP4 and ACE2 expression (P<0.05). Conclusions DPP4 and ACE2 proteins are lowly expressed in the pulmonary sarcoidosis group and pulmonary bullae group, while their expression level is high in COVID-19 and COPD groups. There is no significant difference in the expression level of DPP4 and ACE2 protein in the COVID-19 and COPD lung tissues. There may be a positive correlation between DPP4 and ACE2 proteins expression in lung tissue, and smoking may be a potential risk factor for COVID-19.