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Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1

查看全文 作  者:Atsushi [1]Iraha;Hiroshi [2]Chinen;Akira [1]Hokama;Takumi [3]Yonashiro;Tetsu [2]Kinjo;Kazuto [1]Kishimoto;Manabu [2]Nakamoto;Tetsuo [1]Hirata;Nagisa [2]Kinjo;Futoshi [1]Higa;Masao [1]Tateyama;Fukunori [2]Kinjo;Jiro [1]Fujita 高影响力作者 机构地区:[1]Department of Infectious,Respiratory,and Digestive Medicine,Faculty of Medicine,University of the Ryukyus;[2]Department of Endoscopy,University of the Ryukyus Hospital;[3]Uruma Bio Co Ltd高影响力机构 出  处:《World Journal of Gastroenterology》索引2013年第19卷第33期,共8页高影响力期刊 摘  要: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-labeled4-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 H2O2treatment,fucoidan significantly increased the TER compared to control(P<0.05),indicating a direct enhancement of intestinal epithelial barrier function.Next,H2O2disrupted the epithelial barrier function in a time-dependent manner.Fucoidan prevented the H2O2-induced destruction in a dosedependent manner.Fucoidan significantly decreased H2O2-induced FD4 flux(P<0.01),indicating the prevention of disruption in paracellular permeability.RTPCR showed that Caco-2 cells endogenously expressed claudin-1 and-2,and occludin and that H2O2reduced 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.H2O2disrupted 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. 关 键 词:FUCOIDAN TIGHT JUNCTION Intestinal EPITHELIAL cells Oxidative stress Inflammatory BOWEL diseases
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