Expression of ACE2 and TMPRSS2 proteins in the upper and lower aerodigestive tracts of rats

Abstract

Objective Patients with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit not only respiratory symptoms but also symptoms of chemo-sensitive disorders and kidney failure. Cellular entry of SARS-CoV-2 depends on the binding of its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike protein-priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 are considered to enhance the invading capacity of SARS-CoV-2.Methods To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, lung, and kidney of rats through immunohistochemistry.Results Strong co-expression of ACE2 and TMPRSS2 proteins was observed in the nasal respiratory epithelium, trachea, bronchioles, alveoli, kidney, and taste buds of the tongue. Remarkably, TMPRSS2 expression was much stronger in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID-19, such as the loss of taste, loss of olfaction, respiratory dysfunction, and acute nephropathy.Conclusions A wide range of organs have been speculated to be affected by SARS-CoV-2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID-19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID-19.Level of Evidence NACompeting Interest StatementThe authors have declared no competing interest.View Full Text