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Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation
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....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039833/ https://www.ncbi.nlm.nih.gov/pubmed/32116419 http://dx.doi.org/10.3748/wjg.v26.i7.717 |
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author | Zhang, Yi-Chao Chen, Bao-Xiang Xie, Xiao-Yu Zhou, Yan Qian, Qun Jiang, Cong-Qing |
author_facet | Zhang, Yi-Chao Chen, Bao-Xiang Xie, Xiao-Yu Zhou, Yan Qian, Qun Jiang, Cong-Qing |
author_sort | Zhang, Yi-Chao |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7039833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-70398332020-02-28 Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation Zhang, Yi-Chao Chen, Bao-Xiang Xie, Xiao-Yu Zhou, Yan Qian, Qun Jiang, Cong-Qing World J Gastroenterol Basic Study 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. Baishideng Publishing Group Inc 2020-02-21 2020-02-21 /pmc/articles/PMC7039833/ /pubmed/32116419 http://dx.doi.org/10.3748/wjg.v26.i7.717 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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. |
spellingShingle | Basic Study Zhang, Yi-Chao Chen, Bao-Xiang Xie, Xiao-Yu Zhou, Yan Qian, Qun Jiang, Cong-Qing Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation |
title | Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation |
title_full | Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation |
title_fullStr | Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation |
title_full_unstemmed | Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation |
title_short | Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation |
title_sort | role of tenascin-x in regulating tgf-β/smad signaling pathway in pathogenesis of slow transit constipation |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039833/ https://www.ncbi.nlm.nih.gov/pubmed/32116419 http://dx.doi.org/10.3748/wjg.v26.i7.717 |
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