Reference - Detail
|Author||Iraha A, Chinen H, Hokama A, Yonashiro T, Kinjo T, Kishimoto K, Nakamoto M, Hirata T, Kinjo N, Higa F, Tateyama M, Kinjo F, Fujita J.|
|Title||Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1.|
|Journal||World J Gastroenterol|
AIM:To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.
METHODS:In Caco-2 cell monolayer models, the disruption of barrier function by oxidative stress is mediated by H₂O₂. The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance (TER) and permeability was estimated by measuring the paracellular transport of FITC-labeled 4-kDa dextran (FD4). The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux. The expression of tight junction (TJ) proteins was assessed using reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining.
RESULTS:Without H₂O₂ treatment, fucoidan significantly increased the TER compared to control (P < 0.05), indicating a direct enhancement of intestinal epithelial barrier function. Next, H₂O₂ disrupted the epithelial barrier function in a time-dependent manner. Fucoidan prevented the H₂O₂-induced destruction in a dose-dependent manner. Fucoidan significantly decreased H₂O₂-induced FD4 flux (P < 0.01), indicating the prevention of disruption in paracellular permeability. RT-PCR showed that Caco-2 cells endogenously expressed claudin-1 and -2, and occludin and that H₂O₂ reduced the mRNA expression of these TJ proteins. Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin. Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface. H₂O₂ disrupted the integrity of claudin-1. Treatment with fucoidan dramatically attenuated the expression of claudin-1.
CONCLUSION:Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1. Thus, fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.
|MeSH||Anti-Ulcer Agents / pharmacology* Anti-Ulcer Agents / therapeutic use Caco-2 Cells Claudin-1 / metabolism* Drug Evaluation, Preclinical Epithelial Cells / drug effects Humans Hydrogen Peroxide Inflammatory Bowel Diseases / drug therapy Intestinal Mucosa / drug effects* Polysaccharides / pharmacology* Polysaccharides / therapeutic use Tight Junctions / drug effects* Up-Regulation / drug effects|
|WOS Category||GASTROENTEROLOGY & HEPATOLOGY|
|Human and Animal Cells|