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Empagliflozin (EMPA) is a sodium-glucose co-transporter\u00a02 inhibitor used in treatment of type\u00a02 diabetes mellitus. Interleukin-6\/Janus kinase\/signal transducer and activator of transcription\u00a03 (IL-6\/JAK\/STAT3) signaling pathway is essential in driving inflammation, fibrosis, and epithelial\u2013mesenchymal transition (EMT). Tracheal basal stem cells are responsible for epithelial regeneration after injury. This study aimed to investigate the potential protective effects of EMPA against LPS-induced tracheal injury, with emphasis on EMT and tracheal basal stem cells. Sixty adult male rats were allocated into four groups: control; EMPA, which received EMPA (10\u00a0mg\/kg\/day) via oral gavage for 28\u00a0days; LPS, which received single intratracheal dose of LPS (5\u00a0mg\/kg) on day\u00a01; and LPS\u2009+\u2009EMPA, which received single LPS dose and EMPA for 28\u00a0days. Tracheal specimens were processed for biochemical, histological, immunohistochemical and RT-quantitative real-time PCR analysis. Compared to the LPS group, the LPS\u2009+\u2009EMPA group showed marked improvement of histological, ultrastructural ,and biochemical alterations including maintenance of epithelial and cilia integrity, decreased lipid peroxidation, stimulated antioxidant enzyme activities, reduced serum inflammatory cytokines, increased percentage area of E-cadherin (an epithelial marker) immunostaining, decreased percentage area of fibrosis, vimentin (a mesenchymal marker), and pro-apoptotic Bax; and enhanced percentage area of cytokeratin\u00a05\/6 (CK5\/6) (stem cell marker). Moreover, EMPA downregulated the IL-6\/JAK\/STAT3 pathway involved in EMT. In conclusion, EMPA alleviated LPS-induced tracheal injury through its antioxidant and anti-inflammatory properties, downregulation of IL-6\/JAK\/STAT3 signaling pathway, and preservation of the tracheal basal stem cells.<\/jats:p>","DOI":"10.1007\/s00418-026-02531-4","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:38:01Z","timestamp":1788615481000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Empagliflozin mitigates lipopolysaccharide-induced tracheal injury in rats via downregulation of IL-6\/JAK\/STAT3 signaling pathway and stem cell preservation: histological and molecular study"],"prefix":"10.1007","volume":"164","author":[{"given":"Nahla Reda","family":"Sarhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally A.","family":"Elekhtiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Elmowafy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira I.","family":"Shrief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"issue":"2","key":"2531_CR1","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1097\/MS9.0000000000004512","volume":"88","author":"O Abunada","year":"2026","unstructured":"Abunada O, Hassan F, Kumar N, Kumar S, Majeed I, Batra K, Kumar D, Deepika D, Turesh M, Ashraf T, Hyder S, Suresh KN, Kumar L, Kumar S, Kamlesh F, Yusuf SA (2026) Efficacy and safety of SGLT2 inhibitor empagliflozin in T2DM with established cardiovascular disease: a systematic review and meta-analysis of RCTs. 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