Role and Mechanism of Colon Circadian Clock Gene Bmal1 Involved in Symptoms of Irritable Bowel Syndrome With Diarrhea
10.3969/j.issn.1008-7125.2021.07.002
- Author:
Yanjun WANG
1
;
Weiwei ZENG
1
;
Jianru ZHU
1
;
Jing WANG
1
;
Dongfeng CHEN
1
;
Min YANG
1
;
Suxia LI
2
;
Tianwei DENG
3
Author Information
1. Department of Gastroenterology, Daping Hospital, Army Medical Center, Army Medical University
2. National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University
3. Department of Gastroenterology, The Three Gorges Hospital of Chongqing University
- Publication Type:Journal Article
- Keywords:
5-Hydroxytryptamine;
Bmal1;
Circadian Clocks;
Diarrhea;
Enterochromaffin Cells;
Irritable Bowel Syndrome
- From:
Chinese Journal of Gastroenterology
2021;26(7):389-394
- CountryChina
- Language:Chinese
-
Abstract:
Background: Symptoms of irritable bowel syndrome with diarrhea (IBS-D) are known to be influenced by circadian oscillation; however, the pathophysiological mechanism is still unclear. Aims: To investigate the role and underlying mechanism of colon circadian clock gene Bmal1 involved in the occurrence of symptoms in IBS-D patients. Methods: Forty-six patients with IBS-D and 34 normal controls from Army Medical Center of PLA during September 2018 to February 2021 were recruited in this study. IBS-severity scoring system (IBS-SSS) was used to evaluate the severity of IBS-D symptoms. A colonoscopy was performed to obtain biopsy specimens from rectosigmoid colon. The concentration of 5-hydroxytryptamine (5-HT), and expressions of Bmal1 and chromogranin A (CgA), a biomarker of enterochromaffin cells (EC cells), in colonic mucosa were detected by ELISA and double-labeled immunofluorescence, respectively. Results: Both the 5-HT concentration and number of EC cells in colonic mucosa of IBS-D patients were significantly higher than those of the normal controls (all P< 0.05). Bmal1 was mainly expressed in intestinal epithelial cells and was highly expressed in EC cells. Co-expression of Bmal1 and CgA was observed. Compared with the normal control group biopsied at the same time point, expression of Bmal1 was significantly higher in specimens taken at 9 a.m., and expression of Bmal1 was significantly lower in specimens taken at 17 p.m. in IBS-D patients (all P< 0.05). Spearman correlation coefficient analysis showed that Bmal1 expression at 9 a.m. was positively correlated with the total score of IBS-SSS and subscore of abdominal pain and discomfort (r
