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Updated: Sep 18, 2025

In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
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Role of C-Jun N-Terminal Kinases on a Stressed Epithelium: Time for Testing Isoform Specificity

Nitesh Shashikanth1, Osama Alaidi2, Lohitha Basa1

  • 1Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38103, USA.

Biology
|June 26, 2025
PubMed

Insights

Stressors trigger cellular responses via the sympathetic nervous system and c-Jun-N-terminal kinases (JNK). This review examines JNK1 and JNK2 roles in cellular stress, particularly in the gut, and the need for isoform-specific inhibitors.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Stress Physiology

Background:

  • Biological, physiological, and psychological stressors activate the body's stress response.
  • Stressors trigger hormonal pathways like the SAM and HPA axis, and can directly damage organs.
  • Cellular equilibrium is disrupted by stressors, leading to reactive oxygen species (ROS) and damage.

Purpose of the Study:

  • To review the roles of c-Jun-N-terminal kinases (JNK), specifically JNK1 and JNK2, in cellular stress responses.
  • To focus on JNK1 and JNK2 involvement in gastrointestinal tract epithelial cells, including tight junction and cytoskeletal changes.
  • To explore the dual roles of JNK1 and JNK2 in promoting cell survival versus apoptosis and the potential for isoform-specific inhibitors.

Main Methods:

  • Review of existing literature on JNK signaling pathways in response to various stressors.
  • Focus on JNK1 and JNK2 ubiquity and specific effects on gastrointestinal epithelial cells.
  • Analysis of JNK protein structure and implications for inhibitor development.

Main Results:

  • JNK signaling pathways, particularly JNK1 and JNK2, are crucial in responding to diverse stressors.
  • JNK1 and JNK2 influence gastrointestinal epithelial cell integrity, affecting tight junctions and cytoskeleton.
  • JNK1 and JNK2 exhibit opposing roles in determining cell fate, promoting either survival or apoptosis.

Conclusions:

  • JNK1 and JNK2 are key mediators of cellular stress responses across various cell types, including the gut epithelium.
  • Understanding the differential roles of JNK1 and JNK2 is critical for addressing diseases linked to stress.
  • Development of JNK-isoform-specific inhibitors is needed for therapeutic intervention in diseases like cancer, obesity, and diabetes.
Keywords:
c-Jun N-terminal Kinase (JNK)epitheliuminhibitorskinasereactive oxygen speciesstressorstructure–function relationship

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