{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:28:14Z","timestamp":1785414494400,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Institutes of T\u00fcrkiye","award":["28528"],"award-info":[{"award-number":["28528"]}]},{"DOI":"10.13039\/501100005378","name":"Scientific Research Projects Coordination Unit of Hacettepe University","doi-asserted-by":"publisher","award":["THD-2024-20721"],"award-info":[{"award-number":["THD-2024-20721"]}],"id":[{"id":"10.13039\/501100005378","id-type":"DOI","asserted-by":"publisher"}]},{"award":["THD-2024-20721"],"award-info":[{"award-number":["THD-2024-20721"]}],"id":[{"id":"https:\/\/ror.org\/04kwvgz42","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The renin\u2013angiotensin system (RAS) regulates inflammation, tissue homeostasis, and barrier integrity in lung and colon epithelial cells. Beyond classical pathways, non-canonical components including angiotensin-converting enzyme 2 (ACE2), epidermal growth factor receptor (EGFR), insulin-like growth factor 2 receptor (IGF2R) and aminopeptidase N (ANPEP) are implicated in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and bacterial sepsis due to their roles in tissue repair and signaling. Despite their similar inflammatory and coagulopathic features, their impact on RAS-associated non-immune gene expression in epithelial tissues remains unclear. This study investigates the regulation of these targets in lung (BEAS-2B) and colon (CRL-1831) cells following exposure to recombinant SARS-CoV-2 spike protein N-terminal domain fragment (S1-NTD) and Pseudomonas aeruginosa-derived lipopolysaccharide (LPS). Cells were treated with 100 ng\/mL of S1-NTD or LPS for 12\u201372 h. Viability was assessed via XTT assays, and molecular changes were analyzed through qRT-PCR and Western blotting. Both stimuli induced a time and dose-dependent decrease in metabolic activity. ACE2 was significantly downregulated in lung cells, while transient upregulation occurred in colon cells at 24 h. EGFR expression increased in colon cells following LPS exposure but decreased in lung cells after S1-NTD treatment. Both IGF2R and ANPEP were upregulated by S1-NTD in lung cells at 72 h, whereas colon cells showed earlier upregulation at 24\u201348 h. Our findings reveal that viral and bacterial stimuli elicit distinct, tissue-specific regulatory patterns in RAS-associated pathways. These alterations may contribute to epithelial barrier dysfunction and inflammation, highlighting these proteins as potential targets for managing secondary bacterial infections and inflammatory lung\u2013gut complications in COVID-19.<\/jats:p>","DOI":"10.3390\/pathogens15060593","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:26Z","timestamp":1780454246000},"page":"593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathogen-Specific Regulation of Renin\u2013Angiotensin System Genes in Epithelial Cells: A Comparative Study of SARS-CoV-2 Spike Protein N-Terminal Domain Fragment and Bacterial Lipopolysaccharide"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9541-9853","authenticated-orcid":false,"given":"Aysegul","family":"Y\u0131lmaz","sequence":"first","affiliation":[{"name":"Medical Microbiology Department, Faculty of Medicine, Lokman Hekim University, Ankara 06510, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-4173","authenticated-orcid":false,"given":"Seyhan","family":"Turk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-4895","authenticated-orcid":false,"given":"Umit Yavuz","family":"Malkan","sequence":"additional","affiliation":[{"name":"Department of Hematology, Faculty of Medicine, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8028-9462","authenticated-orcid":false,"given":"\u0130brahim Celalettin","family":"Haznedaroglu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Faculty of Medicine, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1787-9755","authenticated-orcid":false,"given":"Safiye","family":"Gocer","sequence":"additional","affiliation":[{"name":"Medical Microbiology Department, Faculty of Medicine, Lokman Hekim University, Ankara 06510, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-3621","authenticated-orcid":false,"given":"Sukru Volkan","family":"Ozguven","sequence":"additional","affiliation":[{"name":"Medical Microbiology Department, Faculty of Medicine, Lokman Hekim University, Ankara 06510, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1514-7294","authenticated-orcid":false,"given":"Can","family":"Turk","sequence":"additional","affiliation":[{"name":"Medical Microbiology Department, Faculty of Medicine, Lokman Hekim University, Ankara 06510, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41579-022-00713-0","article-title":"SARS-CoV-2 pathogenesis","volume":"20","author":"Lamers","year":"2022","journal-title":"Nat. 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