title: [Changes of adherens junctions between the epithelial cells of intestinal mucosal barrier in irritable bowel syndrome].
abstract: Objective:To investigate whether there are changes in adherens junctions(AJ), including E-cadherin (E-cad) and β-catenin (β-cat), in the colonic mucosa of irritable bowel syndrome (IBS).Methods:Colorectal dilatation combined with restraint stress was used to establish IBS SD rat model. There were 8 rats in the model group and 8 rats in normal control group. From each rat, the colon tissue 5 centimeters away from ileocecum (I) and the junction of the rectum and sigmoid colon (R) were taken, in which E-cad and β-cat mRNA, protein level and structural changes were detected using real-time quantitative-PCR, Western blot, and immunofluorescence. According to the Rome Ⅲ criteria, IBS with diarrhea (IBS-D) patients receiving colonoscopy (n=17) and healthy volunteers (n=17) were enrolled in Center of Endoscopy of the First Affiliated Hospital of Zhejiang Chinese Medicine University. The colon tissues of I and R locations were collected from them. Colonic epithelial cell AJ protein expression and AJ structural changes in the tissues were detected using Western blot, immunofluorescence and transmission electron microscope (TEM).Results:(1)Both in I and R sites, the mRNA and protein expression of E-cad in IBS rats were both significantly lower than in normal SD rats (allP<0.05). The mRNA expression of β-cat showed no significant change in IBS SD rats compared with the normal SD rats; the protein expression of β-cat was decreased in I(P<0.05), no significantly different in R. (2)In I and R of IBS-D patients, the expression of E-cad protein were significantly decreased(I: 0.85±0.30 vs 1.24±0.34,P=0.00; R: 0.86±0.17 vs 1.14±0.48,P=0.05); the protein expression of β-cat also showed significant reduction both in I(0.85±0.39 vs 1.22±0.51,P=0.04)and R (0.92±0.22 vs 1.16±0.31,P=0.02) of IBS-D patients, compared with the healthy controls. Immunofluorescence results showed that E-cad and β-cat in colonic epithelial cells of I and R in the healthy controls were distributed along the cell membrane, demonstrating honeycomb linear fluorescence; however, in IBS-D patients, the structure of E-cad and β-cat were fuzzy, with disrupted distribution in the cytoplasm. Under TEM, the gaps of AJ in I and R of IBS-D patients appeared wider than in the healthy volunteers.Conclusions:In IBS-D patients, there are wider gaps of AJ, and decreased expression with structural disorder of E-cad and β-cat in the colon. The change of AJ plays an important role in the damage of colonic mucosal barrier and the increase of intestinal epithelial permeability in IBS-D patients, but the mechanism is yet to be further explored.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou 310006, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: S S
authors.initials: SS
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Lü
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D022005:Adherens Junctions / Q000473:pathology*; D000818:Animals; D003106:Colon; D004847:Epithelial Cells; D007413:Intestinal Mucosa; D043183:Irritable Bowel Syndrome / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Adherens junction; E-cadherin; Irritable bowel syndrome; β-catenin