RRC ID 44632
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
Abstract 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.
Volume 19(33)
Pages 5500-7
Published 2013-9-7
DOI 10.3748/wjg.v19.i33.5500
PMID 24023493
PMC PMC3761103
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
IF 3.411
Times Cited 25
Human and Animal Cells