Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2020; 26(46): 7352-7366
Published online Dec 14, 2020. doi: 10.3748/wjg.v26.i46.7352
Colonic vitamin D receptor expression is inversely associated with disease activity and jumonji domain-containing 3 in active ulcerative colitis
Hong-Qian Wang, Wen-Hui Zhang, Ya-Qi Wang, Xiao-Pan Geng, Ming-Wei Wang, Yuan-Yuan Fan, Jing Guan, Ji-Long Shen, Xi Chen
Hong-Qian Wang, Wen-Hui Zhang, Ya-Qi Wang, Xiao-Pan Geng, Ming-Wei Wang, Yuan-Yuan Fan, Jing Guan, Xi Chen, Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Ji-Long Shen, Department of Pathogen Biology, Anhui Medical University, Hefei 230032, Anhui Province, China
Author contributions: Wang HQ collected the data, performed the statistical analysis and drafted the manuscript; Zhang WH, Wang YQ and Geng XP participated in the acquisition of the data; Wang MW and Fan YY provided serum and tissue samples; Guan J generated the tables and figures; Shen JL and Chen X designed the study and revised the manuscript.
Supported by The Key Projects of Natural Science Research of Anhui Province in China, No. 201904a07020043.
Institutional review board statement: The study was approved by the ethics committee of the First Affiliated Hospital of Anhui Medical University (No. PJ2019-14-23).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: None of the authors has any conflicts of interest to declare.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xi Chen, PhD, Professor, Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui Province, China. ayfychenxi@163.com
Received: September 27, 2020
Peer-review started: September 27, 2020
First decision: October 17, 2020
Revised: October 28, 2020
Accepted: November 4, 2020
Article in press: November 4, 2020
Published online: December 14, 2020
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.

Keywords: Vitamin D, Ulcerative colitis, Disease activity, Vitamin D receptor, Jumonji domain-containing 3, Trimethylated H3 lysine 27

Core Tip: This is the first report of the relationship between serum vitamin D, vitamin D receptor (VDR), Jumonji domain-containing 3 (Jmjd3) and trimethylated H3 lysine 27 expression and pathological activity in patients with active ulcerative colitis (UC). In active UC, vitamin D level was negatively correlated with disease activity and positively correlated with VDR expression. Furthermore, colonic Jmjd3 expression was significantly increased, while trimethylated H3 lysine 27 was decreased in UC patients compared to controls. These findings indicate that VDR expression was inversely related to Jmjd3 expression and disease activity in the colonic mucosa of patients with UC.