title: Role of regenerating gene I in claudin expression and barrier function in the small intestine.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kitayama
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. Electronic address: hfukui@hyo-med.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fukui
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Hara
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Eda
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Kodani
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan; Department of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan; Department of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Yamagishi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Watari
authors.affiliation: Department of Biochemistry, Nara Medical University, Kashihara, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D057167:Claudins / Q000378:metabolism*; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D051847:Lithostathine / Q000378:metabolism*; D018345:Mice, Knockout; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: D057167:Claudins; D051847:Lithostathine; C497617:REG1A protein, human; C497615:Reg1 protein, mouse; D016329:Sp1 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases