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Akt inhibitor triciribine (TCBN) has demonstrated promising results in promoting recovery from advanced\u2010stage acute lung injury in preclinical studies. In the current study, we tested the direct effect of TCBN on ACE2 expression in human bronchial (H441) and lung alveolar (A549) epithelial cells. Treatment with TCBN resulted in the downregulation of both messenger RNA and protein levels of ACE2 in A549 cells. Since HMGB1 plays a vital role in the inflammatory response in COVID\u201019, and because hyperglycemia has been linked to increased COVID\u201019 infections, we determined if HMGB1 and hyperglycemia have any effect on ACE2 expression in lung epithelial cells and whether TCBN has any effect on reversing HMGB1\u2010 and hyperglycemia\u2010induced ACE2 expression. We observed increased ACE2 expression with both HMGB1 and hyperglycemia treatment in A549 as well as H441 cells, which were blunted by TCBN treatment. Our findings from this study, combined with our previous reports on the potential benefits of TCBN in the treatment of acute lung injury, generate reasonable optimism on the potential utility of TCBN in the therapeutic management of patients with COVID\u201019.<\/jats:p>","DOI":"10.1002\/jcp.30343","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T09:18:50Z","timestamp":1614158330000},"page":"6597-6606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Akt\u2010independent effects of triciribine on ACE2 expression in human lung epithelial cells: Potential benefits in restricting SARS\u2010CoV2 infection"],"prefix":"10.1002","volume":"236","author":[{"given":"Mir S.","family":"Adil","sequence":"first","affiliation":[{"name":"Clinical and Experimental Therapeutics, Department of Clinical and Administrative Pharmacy, College of Pharmacy, and Charlie Norwood VA Medical Center University of Georgia  Augusta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arti","family":"Verma","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, Department of Clinical and Administrative Pharmacy, College of Pharmacy, and Charlie Norwood VA Medical Center University of Georgia  Augusta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhuri","family":"Rudraraju","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, Department of Clinical and Administrative Pharmacy, College of Pharmacy, and Charlie Norwood VA Medical Center University of Georgia  Augusta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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