c-Jun N-Terminal Kinase-2 Mediates Alcohol and Corticosterone-Induced Tissue Injury at the Gut-Liver Axis.

Authors

Lohitha Basa, Nitesh Shashikanth, Pradeep K Shukla, Chandra Shekhar, Avtar S Meena, Nathan Jones, Preeti Raju, Christopher Nguyen, Samhitha Swarna, Nathaniel B Willis, Siddabasave Gowda B Gowda, Sue-Chin Lee, Joseph F Pierre, RadhaKrishna Rao

Published in

FASEB journal : official publication of the Federation of American Societies for Experimental Biology. Volume 40. Issue 20. Pages e72375. Oct 31, 2026.

Abstract

Chronic stress and the stress hormone corticosterone are exacerbating factors in alcohol-induced gut and liver injury; however, the underlying mechanisms are poorly defined. This study investigates the potential role of c-Jun N-terminal kinase 2 (JNK2) in alcohol- and corticosterone-mediated gut and liver injury. The effects of chronic ethanol feeding and corticosterone administration on gut and liver injury were evaluated in JNK2 knockout (JNK2-KO) and wild-type mice. We measured gut permeability to FITC-inulin in vivo; 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-induced gut barrier dysfunction, epithelial TJ disruption, and colonic mucosal inflammatory responses were potentiated by corticosterone in the wild-type mice, but not in JNK2-KO mice. Microbiota analyses indicated that the gut microbiota composition in pair-fed and ethanol-fed JNK2-KO mice is distinctly different from that of wild-type mice. The effects of ethanol and its potentiation by corticosterone on Paneth cell-specific genes were absent in JNK2-KO mice. Ethanol-induced intestinal mucosal inflammatory responses, endotoxemia, and systemic inflammation, and their potentiation by corticosterone, were absent in JNK2-KO mice. Ethanol-induced liver injury and its potentiation by corticosterone, as assessed by plasma AST/ALT, liver triglyceride, histopathology, and cytokine expression, were also absent in JNK2-KO mice. These data demonstrate that JNK2 plays a pivotal role in ethanol-induced tissue injury at the Gut-Liver axis and that this effect is potentiated by corticosterone.

PMID:
42895205
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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