Dexmedetomidine Protects Intestinal Mucosal Barrier via Activating the α7-nAChR-GDNF in Enteric Glial Cells
YUANHONG MAO#, YUNLAN YANG#, KUN YANG§, YONGQIANG SUN, KUN YANG*,,*
Department of Anaesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, China
* Corresponding Author: KUN YANG. Email: 
# These authors contributed equally to this paper
§ The two authors named “Kun Yang” are different individuals
BIOCELL https://doi.org/10.32604/biocell.2026.075138
Received 25 October 2025; Accepted 27 December 2025; Published online 26 January 2026
Abstract
Objective: Intestinal barrier disruption is a critical event in sepsis and ischemia–reperfusion (I/R) injury. Enteric glial cells (EGCs) maintain barrier integrity by secreting glial cell line–derived neurotrophic factor (GDNF). This study aimed to determine whether Dexmedetomidine (Dex) protects the intestinal barrier via α7-nicotinic acetylcholine receptor (α7-nAChR) signaling in EGCs.
Methods: An
in vitro EGC-intestinal epithelial cell (IEC) co-culture system and a murine intestinal I/R model were established. EGCs were selectively ablated
in vivo using benzalkonium chloride (BAC). Barrier integrity was evaluated by transmembrane electrical resistance (TEER) and plasma FITC-dextran permeability. Enzyme-Linked Immunosorbent Assay (ELISA) and Western blotting quantified levels of GDNF and Occludin. The α7-nAChR antagonist methyllycaconitine (MLA) was applied for mechanistic validation.
Results: In vitro, Dex (40–100 μm) dose-dependently increased GDNF expression in EGCs (
p < 0.05) and enhanced IEC TEER. These protective effects were abolished by MLA pre-treatment (
p < 0.05).
In vivo, Dex significantly reduced I/R-induced mucosal injury and decreased plasma FITC-dextran concentrations compared to the untreated I/R group (0.30 ± 0.01 vs. 0.43 ± 0.02 mg/mL,
p < 0.05). Notably, in EGC-ablated mice, Dex failed to restore Occludin levels or reduce permeability (
p > 0.05), confirming EGC-dependence.
Conclusion: Dexmedetomidine protects the intestinal mucosal barrier via an EGC-dependent mechanism involving α7-nAChR activation and GDNF-mediated tight junction reinforcement. These findings highlight EGCs as key effectors of Dex-induced intestinal protection and potential therapeutic targets for barrier dysfunction in critical illness.
Keywords
Dexmedetomidine; enteric glial cells; α7-nicotinic acetylcholine receptor; glial cell line–derived neurotrophic factor (GDNF); intestinal barrier
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