ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by a JNK-2-, c-Src-, and MLCK-dependent mechanism.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
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- Role of C-Jun N-Terminal Kinases on a Stressed Epithelium: Time for Testing Isoform Specificity.Biology · 2025Review
- A stretchable human lung-on-chip model of alveolar inflammation for evaluating anti-inflammatory drug response.Bioengineering & translational medicine · 2025Article
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- The epithelial adherens junction component PLEKHA7 regulates ECM remodeling and cell behavior through miRNA-mediated regulation of MMP1 and LOX.bioRxiv : the preprint server for biology · 2024Article
- Effects of SPA4 peptide on lipopolysaccharide-disrupted lung epithelial barrier, injury, and function in a human cell system and mouse model of lung injury.Physiological reports · 2022Article
- The urothelium: a multi-faceted barrier against a harsh environment.Mucosal immunology · 2022Review
- Simple graphical approach to investigate differences in transepithelial paracellular leak pathway permeability.Physiological reports · 2022Article
- Immune response and pathogen invasion at the choroid plexus in the onset of cerebral toxoplasmosis.Journal of neuroinflammation · 2022Article
- The effects ofPeerJ · 2022Article
- The ProbioticFrontiers in nutrition · 2022Article
- The Epithelial Cell Leak Pathway.International journal of molecular sciences · 2021Review
- Tight Junctions as a Key for Pathogens Invasion in Intestinal Epithelial Cells.International journal of molecular sciences · 2021Review
- Actin cytoskeleton dynamics during mucosal inflammation: a view from broken epithelial barriers.Current opinion in physiology · 2021Article
- A Simple Method to Test Mechanical Strain on Epithelial Cell Monolayers Using a 3D-Printed Stretcher.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Ruffles and spikes: Control of tight junction morphology and permeability by claudins.Biochimica et biophysica acta. Biomembranes · 2020Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The intestinal epithelium is subjected to various types of mechanical stress. In this study, we investigated the impact of cyclic stretch on tight junction and adherens junction integrity in Caco-2 cell monolayers. Stretch for 2 h resulted in a dramatic modulation of tight junction protein distribution from a linear organization into wavy structure. Continuation of cyclic stretch for 6 h led to redistribution of tight junction proteins from the intercellular junctions into the intracellular compartment. Disruption of tight junctions was associated with redistribution of adherens junction proteins, E-cadherin and β-catenin, and dissociation of the actin cytoskeleton at the actomyosin belt. Stretch activates JNK2, c-Src, and myosin light-chain kinase (MLCK). Inhibition of JNK, Src kinase or MLCK activity and knockdown of JNK2 or c-Src attenuated stretch-induced disruption of tight junctions, adherens junctions, and actin cytoskeleton. Paracellular permeability measured by a novel method demonstrated that cyclic stretch increases paracellular permeability by a JNK, Src kinase, and MLCK-dependent mechanism. Stretch increased tyrosine phosphorylation of occludin, ZO-1, E-cadherin, and β-catenin. Inhibition of JNK or Src kinase attenuated stretch-induced occludin phosphorylation. Immunofluorescence localization indicated that phospho-MLC colocalizes with the vesicle-like actin structure at the actomyosin belt in stretched cells. On the other hand, phospho-c-Src colocalizes with the actin at the apical region of cells. This study demonstrates that cyclic stretch disrupts tight junctions and adherens junctions by a JNK2, c-Src, and MLCK-dependent mechanism.
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