Colonic vitamin D receptor expression is inversely associated with disease activity and jumonji domain-containing 3 in active ulcerative colitis

Abstract

BACKGROUND The expression of jumonji domain-containing 3 (Jmjd3) and trimethylated H3 lysine 27 (H3K27me3) in active ulcerative colitis (UC) and the correlation between vitamin D receptor (VDR) and the Jmjd3 pathway are unknown. AIM To study the relationship between VDR, Jmjd3 and H3K27me3 in patients with active UC. METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study. The patients with active UC were divided into groups according to mild (n = 29), moderate (n = 32) and severe (n = 29) disease activity based on the modified Mayo score. Vitamin D levels were measured by radioimmunoassay. Colonic mucosal tissues from UC patients and controls were collected by colonoscopy. The expression of VDR, Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining. RESULTS Patients with active UC had lower levels of serum vitamin D (13.7 ± 2.8 ng/mL, P < 0.001) than the controls (16.2 ± 2.5 ng/mL). In the UC cohort, serum vitamin D level was negatively correlated with disease activity (r = -0.323, P = 0.001). VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues (P < 0.001) and negatively correlated with disease activity (r = -0.868, P < 0.001). Similar results for VDR expression were noted in the most serious lesion (defined as UC diseased) and 20 cm proximal to the anus (defined as UC normal) ( P < 0.05). Simultaneously, Jmjd3 expression significantly increased in UC patients (P < 0.001), but no difference was found between the different sites in UC patients. H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues (P < 0.001), but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients (P < 0.05). Jmjd3 Level was negatively correlated with the level of VDR (r = -0.342, P = 0.002) and H3K27me3 (r = -0.341, P = 0.002), while VDR level was positively correlated with H3K27me3 (r = 0.473, P < 0.001). CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC. Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.