Investigation of distribution of GSK-3β signal pathway by age groups in cases of ulcerative colitis

Abstract

Ulcerative colitis (UC), one of the inflammatory bowel diseases, has been reported to increase in recent years. Although the exact cause is unknown, disruptions in the molecular pathways are thought to trigger UC. We aimed to examine the distributions of glycogen synthase kinase-3beta (GSK-3β), nuclear factor-kappa B (NF-κB) and wingless/int-1 (Wnt-1) in different age groups diagnosed with UC. Patients diagnosed with UC were divided into four groups according to their ages: Group 1, aged 18–30 (n=20); Group 2, aged 31–45 (n=20); Group 3, aged 46–60 (n=20); Group 4, aged 61–75 (n=20). Tissue sections were histochemically stained to examine the parameters of epithelial cell height, length of crypt, thickness of muscularis mucosa and extent of submucosal fibrosis. The immunohistochemistry assay was performed using cell survival and for GSK-3β, NF-κB and Wnt-1 cell growth markers. Immunoreactivities were evaluated using H-score and analyzed using the one-way analysis of variance (ANOVA) test for statistics. It was detected a decrease in the histopathological parameters whereas the immunoreactivities of GSK-3β, NF-κB and Wnt-1 were increased with increasing age. The levels of GSK-3β immunoreactivity were similar in both epithelium and submucosa in all groups. NF-κB immunoreactivity was higher in submucosa of Groups 1, 2 and 3, while Wnt-1 was enhanced in Groups 1 and 3. The results of histopathology showed that the integrity of the epithelial tissue in the colon deteriorated with increasing age. The expressions of GSK-3β, NF-κB and Wnt-1 were detected in all age groups. We thought that there was a synergistic activation between these three markers. Nevertheless, studies are needed to investigate this molecular pathway.

An in vitro model to study immune activation, epithelial disruption and stromal remodelling in inflammatory bowel disease and fistulising Crohn’s disease

“…Striking structural differences were found between control and inflamed IBD mucosal constructs - the latter containing more cuboidal cells that lacked the polarity and epithelial height exhibited by controls. This matches observations in IBD patients and squamous wound-associated epithelial (WAE) cells at areas of epithelial disruption, which are particularly prevalent in fistulising CD during epithelial-to-mesenchymal transition (EMT) ( 53 – 56 ).…”