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This study investigates the potential role of c\u2010Jun N\u2010terminal kinase 2 (JNK2) in alcohol\u2010 and corticosterone\u2010mediated gut and liver injury. The effects of chronic ethanol feeding and corticosterone administration on gut and liver injury were evaluated in JNK2 knockout (JNK2\u2010KO) and wild\u2010type mice. We measured gut permeability to FITC\u2010inulin in\u00a0vivo; epithelial tight junction (TJ) integrity by immunofluorescence confocal microscopy; microbiota dysbiosis by 16S rRNA sequencing; mucosal inflammatory responses by cytokine mRNA assay; endotoxemia by plasma lipopolysaccharide (LPS) levels; systemic inflammation by cytokine ELISA; and liver damage by multiple assays. Data show that chronic ethanol feeding\u2010induced gut barrier dysfunction, epithelial TJ disruption, and colonic mucosal inflammatory responses were potentiated by corticosterone in the wild\u2010type mice, but not in JNK2\u2010KO mice. Microbiota analyses indicated that the gut microbiota composition in pair\u2010fed and ethanol\u2010fed JNK2\u2010KO mice is distinctly different from that of wild\u2010type mice. The effects of ethanol and its potentiation by corticosterone on Paneth cell\u2010specific genes were absent in JNK2\u2010KO mice. Ethanol\u2010induced intestinal mucosal inflammatory responses, endotoxemia, and systemic inflammation, and their potentiation by corticosterone, were absent in JNK2\u2010KO mice. Ethanol\u2010induced liver injury and its potentiation by corticosterone, as assessed by plasma AST\/ALT, liver triglyceride, histopathology, and cytokine expression, were also absent in JNK2\u2010KO mice. These data demonstrate that JNK2 plays a pivotal role in ethanol\u2010induced tissue injury at the Gut\u2010Liver axis and that this effect is potentiated by corticosterone.<\/jats:p>","DOI":"10.1096\/fj.202601355r","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T11:28:28Z","timestamp":1792409308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["c\u2010Jun N\u2010Terminal Kinase\u20102 Mediates Alcohol and Corticosterone\u2010Induced Tissue Injury at the Gut\u2010Liver Axis"],"prefix":"10.1096","volume":"40","author":[{"given":"Lohitha","family":"Basa","sequence":"first","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitesh","family":"Shashikanth","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2515-9766","authenticated-orcid":false,"given":"Pradeep K.","family":"Shukla","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra","family":"Shekhar","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-2488","authenticated-orcid":false,"given":"Avtar S.","family":"Meena","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Jones","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeti","family":"Raju","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Nguyen","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samhitha","family":"Swarna","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel B.","family":"Willis","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddabasave Gowda","family":"B Gowda","sequence":"additional","affiliation":[{"name":"Graduate School of Global Food Resources Hokkaido University  Sapporo Japan"},{"name":"Faculty of Health Sciences Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue\u2010Chin","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Pierre","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-8371","authenticated-orcid":false,"given":"RadhaKrishna","family":"Rao","sequence":"additional","affiliation":[{"name":"College of Medicine University of Tennessee Health Science Center  Memphis Tennessee USA"},{"name":"Lt. 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