Dislocation of Rab13 and vasodilator-stimulated phosphoprotein in inactive colon epithelium in patients with Crohn's disease.
Crohn's disease is associated with increased permeability of the intestine even in quiescent patients. Increased intestinal permeability may cause dysregulated immunological responses in the intestinal mucosa that leads to chronic intestinal inflammation. Tight junction proteins contribute to intestinal permeability, and functional abnormality and dislocation of such proteins may cause increased intestinal permeability. We studied the expression of tight junction proteins Rab13, vasodilator-stimulated phosphoprotein (VASP), zonula occludin-1 (ZO-1), and F-actin in the intestinal epithelium of patients with inactive inflammatory bowel disease. Surgical samples were obtained from 10 controls (without inflammatory bowel disease), 10 patients with Crohn's disease and 7 patients with ulcerative colitis. F-actin was visualized with fluorescent phalloidin. Tight junction proteins were visualized by an immunofluorescence method. Rab13, VASP, and ZO-1 were found in apical tight junctions in normal epithelium but were dislocated to the basolateral position in patients with inactive Crohn's disease, whereas the structure of F-actin was maintained in inactive mucosa. In patients with ulcerative colitis, these tight junction proteins were not dislocated. Latent dislocation of tight junction proteins in the inactive mucosa of patients with Crohn's disease may permit the invasion of gut antigens to initiate and perpetuate altered immune response.
Ohira
Mizuki
M
Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Osaka, Japan.
Oshitani
Nobuhide
N
Hosomi
Shuhei
S
Watanabe
Kenji
K
Yamagami
Hirokazu
H
Tominaga
Kazunari
K
Watanabe
Toshio
T
Fujiwara
Yasuhiro
Y
Maeda
Kiyoshi
K
Hirakawa
Kosei
K
Arakawa
Tetsuo
T
D000328:Adult; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism*; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008875:Middle Aged; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D000098662:Vasodilator-Stimulated Phosphoprotein; C085485:RAB13 protein, human; D020691:rab GTP-Binding Proteins