ArticleThe Biochemical journal2015
Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 102 citations in OpenAlex.
- Article
- Establishment of an In Vitro DSS-Induced Epithelial Injury Model to Investigate Dose-Dependent Effects of IL-6 and Butyrate on Barrier Function.International journal of molecular sciences · 2026Article
- Effect and Mechanisms of Electroacupuncture on Mucosal Healing in Ulcerative Colitis Mice via Non-neuroronal Cholinergic System.Chinese journal of integrative medicine · 2026Article
- Exploring new animal models of ulcerative colitis: evaluating chemical and patient-derived microbial triggers to advance translational relevance.Laboratory animal research · 2026Article
- Oncometabolite 5-IPNature chemical biology · 2026Article
- ST3Gal1 modulates intestinal barrier function and impacts human ulcerative colitis.Molecular medicine reports · 2026Article
- Secondary bile acid lithocholic acid ameliorates colitis-like inflammation in a human intestine-on-chip system.Frontiers in immunology · 2026Article
- Article
- Role of C-Jun N-Terminal Kinases on a Stressed Epithelium: Time for Testing Isoform Specificity.Biology · 2025Review
- NOD1 deficiency promotes inflammation via autophagic degradation of ASK1.Communications biology · 2025Article
- Identification of subtypes and biomarkers associated with disulfidptosis-related ferroptosis in ulcerative colitis.Hereditas · 2025Article
- The Diagnostic Significance of SLC26A2 and Its Potential Role in Ulcerative Colitis.Biomedicines · 2025Article
- Bisdemethoxycurcumin and Curcumin Alleviate Inflammatory Bowel Disease by Maintaining Intestinal Epithelial Integrity and Regulating Gut Microbiota in Mice.Journal of agricultural and food chemistry · 2025Article
- Roles of JNK, ERK, and PI3K/AKT signaling pathways in zinc-mediated alleviation of thermal stress-induced damage to the integrity and barrier function of primary cultured chick jejunal epithelial cells.Journal of animal science · 2025Article
- The Improvement of Intestinal Mucosal Epithelial Barrier Integrity by 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-Journal of inflammation research · 2025Article
- Interferon regulatory factor 7 alleviates the experimental colitis through enhancing IL-28A-mediated intestinal epithelial integrity.Journal of translational medicine · 2024Article
- Cell-permeable JNK-inhibitory peptide regulates intestinal barrier function and inflammation to ameliorate necrotizing enterocolitis.Journal of cellular and molecular medicine · 2024Article
- Live Calcium Imaging of Virus-Infected Human Intestinal Organoid Monolayers Using Genetically Encoded Calcium Indicators.Journal of visualized experiments : JoVE · 2024Article
- New insights into the intestinal barrier through "gut-organ" axes and a glimpse of the microgravity's effects on intestinal barrier.Frontiers in physiology · 2024Review
- CaBiomolecules · 2023Review
6 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
Funding
Abstract
Disruption of intestinal epithelial tight junctions is an important event in the pathogenesis of ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis in mice with symptoms similar to ulcerative colitis. However, the mechanism of DSS-induced colitis is unknown. We investigated the mechanism of DSS-induced disruption of intestinal epithelial tight junctions and barrier dysfunction in Caco-2 cell monolayers in vitro and mouse colon in vivo. DSS treatment resulted in disruption of tight junctions, adherens junctions and actin cytoskeleton leading to barrier dysfunction in Caco-2 cell monolayers. DSS induced a rapid activation of c-Jun N-terminal kinase (JNK), and the inhibition or knockdown of JNK2 attenuated DSS-induced tight junction disruption and barrier dysfunction. In mice, DSS administration for 4 days caused redistribution of tight junction and adherens junction proteins from the epithelial junctions, which was blocked by JNK inhibitor. In Caco-2 cell monolayers, DSS increased intracellular Ca(2+) concentration, and depletion of intracellular Ca(2+) by 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM) or thapsigargin attenuated DSS-induced JNK activation, tight junction disruption and barrier dysfunction. Knockdown of apoptosis signal-regulated kinase 1 (Ask1) or MKK7 blocked DSS-induced tight junction disruption and barrier dysfunction. DSS activated c-Src by a Ca2+ and JNK-dependent mechanism. Inhibition of Src kinase activity or knockdown of c-Src blocked DSS-induced tight junction disruption and barrier dysfunction. DSS increased tyrosine phosphorylation of occludin, zonula occludens-1 (ZO-1), E-cadherin and β-catenin. SP600125 abrogated DSS-induced tyrosine phosphorylation of junctional proteins. Recombinant JNK2 induced threonine phosphorylation and auto-phosphorylation of c-Src. The present study demonstrates that Ca(2+)/Ask1/MKK7/JNK2/cSrc signalling cascade mediates DSS-induced tight junction disruption and barrier dysfunction.
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