Glial cell line-derived neurotrophic factor improves impaired colonic motility in experimental colitis mice through connexin 43.

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. To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43 (Cx43). 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. 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. 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. ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.

Citation

Wei Yang, Rui Liu, Feng Xu. Glial cell line-derived neurotrophic factor improves impaired colonic motility in experimental colitis mice through connexin 43. World journal of gastroenterology. 2025 Feb 28;31(8):100069

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PMID: 40062335

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