@article{Mao2026, 
author = {Yuanhong Mao and Yunlan Yang and Kun Yang and Yongqiang Sun and Kun Yang},
title = {Dexmedetomidine Protects Intestinal Mucosal Barrier via Activating the α7-nAChR-GDNF in Enteric Glial Cells},
year = {2026},
journal = {BIOCELL},
volume = {50},
number = {3},
pages = {11},
keywords = {Dexmedetomidine, enteric glial cells, α7-nicotinic acetylcholine receptor, glial cell line–derived neurotrophic factor (GDNF), intestinal barrier},
url = {https://www.sciopen.com/article/10.32604/biocell.2026.075138},
doi = {10.32604/biocell.2026.075138},
abstract = {ObjectiveIntestinal 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.MethodsAn 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.ResultsIn 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.ConclusionDexmedetomidine 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.}
}