Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2020; 26(7): 717-724
Published online Feb 21, 2020. doi: 10.3748/wjg.v26.i7.717
Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation
Yi-Chao Zhang, Bao-Xiang Chen, Xiao-Yu Xie, Yan Zhou, Qun Qian, Cong-Qing Jiang
Yi-Chao Zhang, Bao-Xiang Chen, Xiao-Yu Xie, Yan Zhou, Qun Qian, Cong-Qing Jiang, Department of Colorectal and Anal Surgery of Zhongnan Hospital of Wuhan University, Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Hubei Key Laboratory of Intestinal and Colorectal Diseases (Zhongnan Hospital of Wuhan University), Colorectal and Anal Disease Research Center of Medical School (Zhongnan Hospital of Wuhan University), Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei Province, Wuhan 430071, Hubei Province, China
Author contributions: Zhang YC and Chen BX contributed equally to this work; Xie XY and Zhou Y collected the clinical tissues after surgery; Qian Q coordinated the research; Jiang CQ designed and coordinated the research.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Zhongnan Hospital of Wuhan University.
Conflict-of-interest statement: The authors declare no financial conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Cong-Qing Jiang, PhD, Professor, Surgeon, Department of Colorectal and Anal Surgery of Zhongnan Hospital of Wuhan University, No. 169, East Lake Road, Wuchang District, Wuhan 430071, Hubei Province, China. wb002554@whu.edu.cn
Received: November 18, 2019
Peer-review started: November 18, 2019
First decision: December 23, 2019
Revised: January 7, 2020
Accepted: January 11, 2020
Article in press: January 11, 2020
Published online: February 21, 2020
Processing time: 94 Days and 18.6 Hours
Abstract
BACKGROUND

Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients. Its incidence rate is 2%-27%. Slow transit constipation (STC) is a common type of chronic functional constipation, accounting for 10.3%-45.5% of such cases. Scholars have performed many studies on the pathogenesis of STC. These studies have indicated that the occurrence of STC may be related to multiple factors, such as dysfunction of the enteric nervous system, interstitial cells of Cajal (ICC) damage, and changes in neurotransmitters regulating intestinal peristalsis.

AIM

To investigate the role of Tenascin-X (TNX) in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.

METHODS

This study included an experimental group and a control group. The experimental group included 28 patients with severe colonic STC, and the control group included 18 patients with normal colon tissues. Immunohistochemistry (IHC) was used to detect c-Kit, a specific marker of the ICC. Western blot, immunofluorescence, and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.

RESULTS

IHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients (22.17 ± 3.28 vs 28.69 ± 3.53, P < 0.05) and that the distribution was abnormal. Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients (c-kit: 0.462 ± 0.099 vs 0.783 ± 0.178, P < 0.01; Smad7: 0.626 ± 0.058 vs 0.799 ± 0.03, P < 0.01) and that TNX and Smad2/3 levels were higher in the STC group (TNX: 0.868 ± 0.028 vs 0.482 ± 0.032, P < 0.01). There was no significant difference in TGF-β between the two groups (0.476 ± 0.028 vs 0.511 ± 0.044, P = 0.272). Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7 (P < 0.05, |R| > 0.8) and TGF-β (P < 0.05, |R| = 0.7).

CONCLUSION

The extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation, leading to an abnormal distribution and dysfunction of ICC in the diseased colon, which promotes the occurrence and development of STC.

Keywords: Slow transit constipation; Tenascin-X; Extracellular matrix glycoproteins; TGF-β

Core tip: The extracellular matrix protein Tenascin-X may activate the TGF-β/Smad signaling pathway by upregulating the Smad2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation, leading to an abnormal distribution and dysfunction of interstitial cells of Cajal in the diseased colon, which promotes the occurrence and development of slow transit constipation.