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

被引：96

作者：

Iraha, Atsushi ^{[1
]}

Chinen, Hiroshi ^{[2
]}

Hokama, Akira ^{[1
]}

Yonashiro, Takumi ^{[3
]}

Kinjo, Tetsu ^{[2
]}

Kishimoto, Kazuto ^{[1
]}

Nakamoto, Manabu ^{[2
]}

Hirata, Tetsuo ^{[1
]}

Kinjo, Nagisa ^{[2
]}

Higa, Futoshi ^{[1
]}

Tateyama, Masao ^{[1
]}

Kinjo, Fukunori ^{[2
]}

Fujita, Jiro ^{[1
]}

机构：

[1] Univ Ryukyus, Fac Med, Dept Infect Resp & Digest Med, Nishihara, Okinawa 9030215, Japan

[2] Univ Ryukyus Hosp, Dept Endoscopy, Okinawa 9030215, Japan

[3] Uruma Bio Co Ltd, Uruma, Okinawa 9042234, Japan

来源：

WORLD JOURNAL OF GASTROENTEROLOGY | 2013年 / 19卷 / 33期

关键词：

Fucoidan; Tight junction; Intestinal epithelial cells; Oxidative stress; Inflammatory bowel diseases; INFLAMMATORY-BOWEL-DISEASE; TIGHT JUNCTION BARRIER; IMMUNE HOMEOSTASIS; IN-VITRO; CACO-2; PERMEABILITY; CELLS; MODEL; PATHOGENESIS; MECHANISMS;

D O I：

10.3748/wjg.v19.i33.5500

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

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-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. RTPCR 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. (c) 2013 Baishideng. All rights reserved.

引用

页码：5500 / 5507

页数：8

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