ArticleThe Journal of clinical investigation2005
Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 247 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
247 citing papers in PubMed, 1 synthesis or guideline pooled it, 412 citations in OpenAlex.
- Bibliometric and visual analysis of human microbiome-breast cancer interactions: current insights and future directions.Frontiers in microbiology · 2024Pooled it
- Gut Microbiota Alter Colonic Expression of Genes Encoding Drug Transporters and Drug-Metabolizing Enzymes in Mice.International journal of molecular sciences · 2026Article
- Bovine Milk-Derived Extracellular Vesicles Ameliorate Steatohepatitis by Restoring Gut Barrier in CDA-HFD-Fed Mice.International journal of molecular sciences · 2026Article
- A special multifiber dietary mixture ameliorates Crohn's-like colitis in an IL-10European journal of nutrition · 2026Article
- The Gut Microbiome in Heart Failure: Pathways to Inflammation and Therapeutic Targets.Metabolites · 2026Review
- Targeting MLCK1 uncouples immune checkpoint inhibitor-induced colitis from antitumour immunity.Gut · 2026Article
- Live tissue microbiota and bacterial translocation: mechanisms and translational perspectives in cardiometabolic diseases.Reviews in endocrine & metabolic disorders · 2026Review
- An endoscopic real-time, in situ assessment of intestinal permeability in type 2 diabetes: links to microbiota and hyperglycemia.Journal of gastroenterology · 2026Article
- The Barrier-Microbiota-Inflammation Axis in Colorectal Cancer: Mechanisms and Emerging Diagnostic & Therapeutic Strategies.Cancers · 2026Review
- Convergent mechanisms of epithelial cell structure manipulation by intestinal pathogens.PLoS pathogens · 2025Review
- The Pathogenesis of Inflammatory Bowel Diseases.The Surgical clinics of North America · 2025Review
- A review of gut failure as a cause and consequence of critical illness.Critical care (London, England) · 2025Review
- Antiedemic Effect of the Myosin Light Chain Kinase Inhibitor PIK7 in the Rat Model of Myocardial Ischemia Reperfusion Injury.Current issues in molecular biology · 2025Article
- Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways.Inflammatory bowel diseases · 2025Review
- Inter-claudin antagonism of paracellular pore function: mechanism and beyond.Tissue barriers · 2025Review
- Potential applications and mechanisms of natural products in mucosal-related diseases.Frontiers in immunology · 2025Review
- Tight junction regulation, intestinal permeability, and mucosal immunity in gastrointestinal health and disease.Current opinion in gastroenterology · 2025Review
- STAT1/MUC4 activation promotes antimicrobial peptide production to reduce intestinal epithelium barrier injury caused by enteropathogenicArchives of medical science : AMS · 2025Article
- Targeting Intestinal Permeability for Graft-versus-Host Disease Treatment: A Therapeutic Perspective with Defibrotide.Journal of experimental pharmacology · 2025Article
- Jianpi Huoxue Decoction Ameliorates Alcohol-associated Liver Disease by Improving Intestinal Barrier Function in Rats.Current medical science · 2024Article
187 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Disruption of the intestinal epithelial barrier occurs in many intestinal diseases, but neither the mechanisms nor the contribution of barrier dysfunction to disease pathogenesis have been defined. We utilized a murine model of T cell-mediated acute diarrhea to investigate the role of the epithelial barrier in diarrheal disease. We show that epithelial barrier dysfunction is required for the development of diarrhea. This diarrhea is characterized by reversal of net water flux, from absorption to secretion; increased leak of serum protein into the intestinal lumen; and altered tight junction structure. Phosphorylation of epithelial myosin II regulatory light chain (MLC), which has been correlated with tight junction regulation in vitro, increased abruptly after T cell activation and coincided with the development of diarrhea. Genetic knockout of long myosin light chain kinase (MLCK) or treatment of wild-type mice with a highly specific peptide MLCK inhibitor prevented epithelial MLC phosphorylation, tight junction disruption, protein leak, and diarrhea following T cell activation. These data show that epithelial MLCK is essential for intestinal barrier dysfunction and that this barrier dysfunction is critical to pathogenesis of diarrheal disease. The data also indicate that inhibition of epithelial MLCK may be an effective non-immunosuppressive therapy for treatment of immune-mediated intestinal disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.