ArticleTissue barriers
Indomethacin induces increase in gastric epithelial tight junction permeability via redistribution of occludin and activation of p38 MAPK in MKN-28 Cells.
Article in Tissue barriers. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- A Non-Pharmacological Paradigm Captures the Complexity in the Mechanism of Action of Poliprotect Against Gastroesophageal Reflux Disease and Dyspepsia.International journal of molecular sciences · 2025Article
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- Network analysis and experimental validation to investigateFrontiers in pharmacology · 2025Article
- In Vitro Protective Effects of a Standardized Extract ofAntioxidants (Basel, Switzerland) · 2024Article
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- Long-Term Use of Proton Pump Inhibitors Disrupts Intestinal Tight Junction Barrier and Exaggerates Experimental Colitis.Journal of Crohn's & colitis · 2023Article
- Differential Effects of Nonsteroidal Anti-Inflammatory Drugs in an In Vitro Model of Human Leaky Gut.Cells · 2023Article
- NMR-Guided Repositioning of Non-Steroidal Anti-Inflammatory Drugs into Tight Junction Modulators.International journal of molecular sciences · 2021Article
- Effects of phenylbutazone alone or in combination with a nutritional therapeutic on gastric ulcers, intestinal permeability, and fecal microbiota in horses.Journal of veterinary internal medicine · 2021Article
- Inhibition of Both Cyclooxygenase-1 and -2 Promotes Epicutaneous Th2 and Th17 Sensitization and Allergic Airway Inflammation on Subsequent Airway Exposure to Protease Allergen in Mice.International archives of allergy and immunology · 2021Article
- Intestinal Barrier Function in Health and Disease-Any role of SARS-CoV-2?Microorganisms · 2020Review
- Influence of kiwifruit on gastric and duodenal inflammation-related gene expression in aspirin-induced gastric mucosal damage in rats.Scientific reports · 2020Article
- Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress.Molecules (Basel, Switzerland) · 2020Article
- Indomethacin Increases the Efficacy of Oxygen Utilization of Colonic Mitochondria and Uncouples Hepatic Mitochondria in Tissue Homogenates From Healthy Rats.Frontiers in medicine · 2020Article
- Catechin and Procyanidin BNutrients · 2019Article
- Indomethacin impairs mitochondrial dynamics by activating the PKCζ-p38-DRP1 pathway and inducing apoptosis in gastric cancer and normal mucosal cells.The Journal of biological chemistry · 2019Article
- Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells.Scientific reports · 2018Article
- Effects of imipenem combined with low-dose cyclophosphamide on the intestinal barrier in septic rats.Experimental and therapeutic medicine · 2018Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tight Junctions (TJ) create a paracellular barrier that is compromised when nonsteriodal anti-inflammatory drugs (NSAIDs) injure the gastric epithelium, leading to increased permeability. However, the mechanism of NSAID-induced gastric injury is unclear. Here, we examined the effect of indomethacin on barrier function and TJ in gastric MKN-28 cells. In concentration response studies, 500 µm indomethacin induced a significant decrease in transepithelial resistance (TER; 380 vs. 220 Ω·cm(2) for control and indomethacin-treated cells respectively, p < 0.05), and increased dextran permeability by 0.2 vs 1.2 g/l (p < 0.05). These changes in barrier function were completely ameliorated by the p38 MAPK inhibitor (SB-203580) but not by JNK inhibitor (SP-600125) or MEK/ERK inhibitor (PD-98059). SiRNA knock down of p38 MAPK prevented the loss of barrier function caused by indomethacin in MKN-28 cells. Western analyses of TJ proteins revealed that expression of occludin was reduced by indomethacin, whereas there was no change in other TJ proteins. The loss of occludin expression induced by indomethacin was prevented by inhibition of p38 MAPK but not JNK or ERK and also by siRNA of p38 MAPK. Immunofluorescence revealed disruption of occludin localization at the site of the tight junction in indomethacin-treated cells, and this was attenuated by inhibition of p38 MAPK. NSAID injury to murine gastric mucosa on Ussing chambers revealed that indomethacin caused a significant drop in TER and increased paracellular permeability. Pretreatment with the p38 MAPK inhibitor significantly attenuated the disruption of barrier function, but JNK and MEK/ERK inhibition had no effect. Western blot analysis on gastric mucosa reveled loss of TJ protein occludin by indomethacin, which was prevented by inhibition of p38 MAPK. This data suggests that indomethacin compromises the gastric epithelial barrier via p38 MAPK inducing occludin alterations in the TJs.
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