{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:16:00Z","timestamp":1789024560703,"version":"build-2803163510"},"reference-count":53,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170093"],"award-info":[{"award-number":["82170093"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670010"],"award-info":[{"award-number":["81670010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:p> Cleavage of the furin site in SARS-CoV-2 spike (S) protein accounts for increased transmissibility of COVID-19 by promoting the entry of virus into host cells through specific angiotensin-converting enzyme 2 (ACE2) receptors. Plasmin, a key serine protease of fibrinolysis system, cleaves the furin site of \u03b3 subunit of human epithelial sodium channels (ENaCs). Sharing the plasmin cleavage by viral S and host ENaC proteins may competitively inter-regulate SARS-CoV-2 transmissibility and edema resolution via the ENaC pathway. To address this possibility, we analyzed single-cell RNA sequence (scRNA-seq) data sets and found that PLAU (encoding urokinase plasminogen activator), SCNN1G (\u03b3ENaC), and ACE2 (SARS-CoV-2 receptor) were co-expressed in airway\/alveolar epithelial cells. The expression levels of PLAU and FURIN were significantly higher compared with TMPRSS2 in healthy group. This difference was further amplified in both epithelial and immune cells in patients with moderate\/severe COVID-19 and SARS-CoV-2 infected airway\/alveolar epithelial cell lines. Of note, plasmin cleaved the S protein and facilitated the entry of pseudovirus in HEK293 cells. 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