Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2025; 31(8): 100069
Published online Feb 28, 2025. doi: 10.3748/wjg.v31.i8.100069
Glial cell line-derived neurotrophic factor improves impaired colonic motility in experimental colitis mice through connexin 43
Wei Yang, Rui Liu, Feng Xu
Wei Yang, Feng Xu, Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Rui Liu, Medical School, Xiangyang Vocational and Technical College, Xiangyang 441021, Hubei Province, China
Author contributions: Yang W contributed to study concept and design and manuscript drafting; Yang W and Liu R contributed to data analysis and interpretation; Xu F contributed to critical revision of the manuscript for important intellectual content; Liu R contributed to statistical analysis; Yang W, Liu R and Xu F contributed to study supervision; All authors have read and approved the manuscript.
Institutional review board statement: This study does not involve any human experiments.
Institutional animal care and use committee statement: Prior to this study, approval for all experimental procedures was obtained from the Institutional Animal Care and Use Committee (approval No. 2022175). Throughout the experiment, every effort was made to minimize the distress of the mice.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon request.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng Xu, MD, Chief Doctor, Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou 450052, Henan Province, China. fengx2024@126.com
Received: August 6, 2024
Revised: December 6, 2024
Accepted: December 25, 2024
Published online: February 28, 2025
Processing time: 169 Days and 17.4 Hours
Abstract
BACKGROUND

Colonic motility dysfunction is a common symptom of ulcerative colitis (UC), significantly affecting patients’ quality of life. Evidence suggests that glial cell line-derived neurotrophic factor (GDNF) plays a role in restoring colonic function.

AIM

To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43 (Cx43).

METHODS

An experimental colitis model was induced in male C57BL/6 mice using dextran sodium sulfate (DSS). The measurement of colonic transit time was conducted, and colon tissues were evaluated through transmission electron microscopy and hematoxylin and eosin staining. The mice were treated with exogenous GDNF and Gap 19, a selective Cx43 inhibitor. The Cx43 and GDNF levels were detected via immunofluorescence, immunohistochemistry, and real-time polymerase chain reaction. The levels of inflammatory markers, including interleukin-1β, tumor necrosis factor-α, interleukin-6, and C-reactive protein, were quantified using enzyme-linked immunosorbent assay.

RESULTS

Experimental colitis was successfully induced using DSS, and the findings exhibited that the colonic transit time was significantly delayed in colitis mice relative to the UC group (P < 0.01). GDNF treatment improved colonic transit time and alleviated intestinal inflammation in DSS-induced colitis mice (P < 0.05). In the UC + Gap19 + GDNF group, colitis symptoms, colonic transit time, and inflammatory marker levels remained comparable to those in the UC group, indicating that the therapeutic effects of GDNF in UC mice were blocked by Gap 19.

CONCLUSION

GDNF improves colonic motility in mice with experimental colitis through a partially Cx43-mediated mechanism. GDNF holds promise as a therapeutic option for improving colonic motility in patients with colitis.

Keywords: Glial cell line-derived neurotrophic factor; Ulcerative colitis; Colonic motility; Connexin 43; Dextran sodium sulfate model

Core Tip: The study investigated the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) in ameliorating impaired colonic motility in a dextran sodium sulfate-induced ulcerative colitis mouse model. The findings revealed that GDNF partially enhanced colonic transit and alleviated intestinal inflammation, with its effects reliant on connexin 43 activity. The findings identified GDNF as a promising candidate for treating abnormal colonic motility in ulcerative colitis patients, highlighting the significance of connexin 43 in its therapeutic mechanism.