Role of Colonic Expression of Wnt Inhibitory Factor-1 in Ulcerative Colitis

Abstract

Introduction: Wnt proteins constitute a family of molecules that are considered to have paramount importance in embryonic development. Recent data suggests that Wnt pathways play a significant role in inflammation, carcinogenesis, and bone development. Wnt inhibitor factor-1 (WIF-1) is a secreted protein that binds to Wnt proteins and inhibits their activity. Our aim was to investigate the colonic expression of WIF-1 in ulcerative colitis (UC). Methods: A total of 24 UC patients were enrolled. Four colon biopsies were obtained during routine surveillance colonoscopy from each patient--2 biopsies from normal-looking areas of colon; and 2 were sampled from inflamed colon. The degree of inflammation in multiple sections of the colon biopsies was graded as I, II, and III by an experienced pathologist. By immunohistochemistry, WIF-1 staining in the glandular region and lamina propria of the colon was graded as I, II, and III based on the percentage of positively stained cells and intensity of staining. The association between inflammation and WIF-1 staining in the multiple colon biopsy sections of UC was studied using Pearson correlation. Results: Of the 24 patients, 70% were males. Mean age was 55.2 years (26-83). WIF-1 staining significantly increased in the lamina propria (p=0.01) and glandular region (p=0.005) with increasing inflammation in UC patients (Figures). On stratification of UC colon biopsy sections in those obtained from normal-looking areas and inflamed-looking areas during colonoscopy, WIF-1 staining was significantly increased in both lamina propria (p= 0.013) and glandular region (p=0.01) in inflamed-looking areas of colon. Conclusion: WIF-1 is increasingly expressed in the inflamed areas of colon in UC patients. WIF-1 may have a crucial role in the pathogenesis of UC; and a potential novel therapeutic strategy may be identified for UC by blocking the WIF-1 in Wnt pathway.Figure 1Figure 2