@Article{biocell.2026.075138,
AUTHOR = {Yuanhong Mao, Yunlan Yang, Kun Yang, Yongqiang Sun, Kun Yang},
TITLE = {Dexmedetomidine Protects Intestinal Mucosal Barrier via Activating the <b>α</b>7-nAChR-GDNF in Enteric Glial Cells},
JOURNAL = {BIOCELL},
VOLUME = {50},
YEAR = {2026},
NUMBER = {3},
PAGES = {--},
URL = {http://www.techscience.com/biocell/v50n3/66714},
ISSN = {1667-5746},
ABSTRACT = { <b>Objective:</b> 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. <b>Methods:</b> An <i>in vitro</i> EGC-intestinal epithelial cell (IEC) co-culture system and a murine intestinal I/R model were established. EGCs were selectively ablated <i>in vivo</i> 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. <b>Results:</b> <i>In vitro</i>, Dex (40–100 μm) dose-dependently increased GDNF expression in EGCs (<i>p</i> &lt; 0.05) and enhanced IEC TEER. These protective effects were abolished by MLA pre-treatment (<i>p</i> &lt; 0.05). <i>In vivo</i>, 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, <i>p</i> &lt; 0.05). Notably, in EGC-ablated mice, Dex failed to restore Occludin levels or reduce permeability (<i>p</i> &gt; 0.05), confirming EGC-dependence. <b>Conclusion:</b> 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.},
DOI = {10.32604/biocell.2026.075138}
}