Faculty Information |
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Article types | Original article |
Language | English |
Refereed paper | Refereed |
Title | Role of regenerating gene I in claudin expression and barrier function in the small intestine. |
Journal | Formal name:Translational research : the journal of laboratory and clinical medicine Abbreviation:Transl Res ISSN code:1878-1810(Electronic)1878-1810(Linking) |
Domestic / Foregin | Foregin |
Volume, Number, Page | 173,pp.92-100 |
Papers・Author | Kitayama Yoshitaka, Fukui Hirokazu, Hara Ken, Eda Hirotsugu, Kodani Mio, Yang Mo, Sun Chao, Yamagishi Hidetsugu, Tomita Toshihiko, Oshima Tadayuki, Watari Jiro, Takasawa Shin, Miwa Hiroto |
Publication date | 2016/07 |
Papers・Description | We have recently shown that loss of the regenerating gene (Reg) I causes susceptibility to nonsteroidal anti-inflammatory drug-induced gastrointestinal damage. However, the mechanism by which Reg I plays a protective role against this pathophysiological condition is unclear. Here, we investigated whether Reg I plays roles in the induction of tight junction proteins and mucosal barrier function in the small intestine. The small-intestinal permeability was evaluated in Reg I-deficient mice by FITC-dextran and transepithelial electrical resistance (TEER) assay. The effect of REG Iα on TEER, claudins expression, and intracellular signaling was examined using Caco2 cells in vitro. Small-intestinal expression of claudins 3 and 4 was investigated in Reg I-deficient mice in vivo. REG I deficiency significantly decreased the expression of claudin 3 in the small-intestinal epithelium. When mice were treated with indomethacin, the serum level of FITC-dextran in Reg I knockout mice was significantly higher than that in wild-type (WT) mice. The level of small-intestinal TEER was significantly decreased in Reg I knockout mice compared with WT mice under normal condition. REG Iα stimulation significantly enhanced the level of TEER in Caco2 cells. Treatment with REG Iα enhanced the expression of claudins 3 and 4 and promoted Sp1, Akt, and ERK phosphorylation in Caco2 cells, whereas these effects were attenuated by treatment with anti-REG Iα antibody. Reg I may play a role in the maintenance of mucosal barrier function by inducing tight junction proteins such as claudins 3 and 4. |
DOI | 10.1016/j.trsl.2016.03.007 |
PMID | 27055226 |