c-Jun N-Terminal Kinase-2 Mediates Alcohol and Corticosterone-Induced Tissue Injury at the Gut-Liver Axis.
5 affiliations
- 1College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
- 2Department of Nutritional Science, University of Wisconsin, Madison, Wisconsin, USA.
- 3Graduate School of Global Food Resources, Hokkaido University, Sapporo, Japan.
- 4Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
- 5Lt. Col. Luke Weathers, Jr. VA Medical Center, Memphis, Tennessee, USA.
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.
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BibTeX
@article{basa2026cjun,
title = {{c-Jun N-Terminal Kinase-2 Mediates Alcohol and Corticosterone-Induced Tissue Injury at the Gut-Liver Axis.}},
author = {Lohitha Basa and Nitesh Shashikanth and Pradeep K Shukla and Chandra Shekhar and Avtar S Meena and Nathan Jones and Preeti Raju and Christopher Nguyen and Samhitha Swarna and Nathaniel B Willis and Siddabasave Gowda B Gowda and Sue-Chin Lee and Joseph F Pierre and RadhaKrishna Rao},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2026},
month = oct,
doi = {10.1096/fj.202601355r},
url = {https://europepmc.org/article/MED/42895205},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - c-Jun N-Terminal Kinase-2 Mediates Alcohol and Corticosterone-Induced Tissue Injury at the Gut-Liver Axis.
AU - Lohitha Basa
AU - Nitesh Shashikanth
AU - Pradeep K Shukla
AU - Chandra Shekhar
AU - Avtar S Meena
AU - Nathan Jones
AU - Preeti Raju
AU - Christopher Nguyen
AU - Samhitha Swarna
AU - Nathaniel B Willis
AU - Siddabasave Gowda B Gowda
AU - Sue-Chin Lee
AU - Joseph F Pierre
AU - RadhaKrishna Rao
PY - 2026
DA - 2026/10/01
JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
DO - 10.1096/fj.202601355r
UR - https://europepmc.org/article/MED/42895205
AB - 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.
SN - 0892-6638
SN - 1530-6860
ER -