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Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways.
Am J Physiol Gastrointest Liver Physiol. 2003 Nov; 285(5):G1028-36.AJ

Abstract

Although the enteric nervous system (ENS) has been shown to regulate various mucosal functions, its role in the physiological control of the human intestinal epithelial barrier is unknown. The aim of this study was to investigate whether the ENS is able to modulate epithelial barrier permeability and a key tight junction-associated protein, zonula occludens-1 (ZO-1). Therefore, we developed a co-culture model, consisting of human submucosa containing the submucosal neuronal network and human polarized colonic epithelial monolayers (HT29-Cl.16E or Caco-2). Submucosal neurons were activated by electrical field stimulation (EFS). Permeability was assessed by measuring the flux of paracellular permeability markers (FITC-dextran or FITC-inulin) across epithelial monolayers. Expression of ZO-1 was determined by immunofluorescence, quantitative immunoblot analysis, and real time RT-PCR. Using the coculture model, we showed that EFS of submucosal neurons resulted in a reduction in FITC-dextran or FITC-inulin fluxes, which was blocked by TTX. In HT29-Cl.16E, the effect of submucosal neuron activation was blocked by a VIP receptor antagonist (VIPra) and reproduced by VIP. Furthermore, ZO-1 expression (mRNA, protein) assessed in HT29-Cl.16E, was significantly increased after submucosal neuron activation by EFS. These effects on ZO-1 expression were blocked by TTX and VIPra and reproduced by VIP. In conclusion, our results strongly suggest a modulatory role of VIPergic submucosal neuronal pathways on intestinal epithelial barrier permeability and ZO-1 expression.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale U 539, Faculté de Médecine, 1, rue Gaston Veil, 44035 Nantes Cedex, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12881224

Citation

Neunlist, Michel, et al. "Human ENS Regulates the Intestinal Epithelial Barrier Permeability and a Tight Junction-associated Protein ZO-1 Via VIPergic Pathways." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 285, no. 5, 2003, pp. G1028-36.
Neunlist M, Toumi F, Oreschkova T, et al. Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. Am J Physiol Gastrointest Liver Physiol. 2003;285(5):G1028-36.
Neunlist, M., Toumi, F., Oreschkova, T., Denis, M., Leborgne, J., Laboisse, C. L., Galmiche, J. P., & Jarry, A. (2003). Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. American Journal of Physiology. Gastrointestinal and Liver Physiology, 285(5), G1028-36.
Neunlist M, et al. Human ENS Regulates the Intestinal Epithelial Barrier Permeability and a Tight Junction-associated Protein ZO-1 Via VIPergic Pathways. Am J Physiol Gastrointest Liver Physiol. 2003;285(5):G1028-36. PubMed PMID: 12881224.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. AU - Neunlist,Michel, AU - Toumi,Ferial, AU - Oreschkova,Tsvetelina, AU - Denis,Marc, AU - Leborgne,Joel, AU - Laboisse,Christian L, AU - Galmiche,Jean-Paul, AU - Jarry,Anne, Y1 - 2003/07/24/ PY - 2003/7/26/pubmed PY - 2003/12/3/medline PY - 2003/7/26/entrez SP - G1028 EP - 36 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 285 IS - 5 N2 - Although the enteric nervous system (ENS) has been shown to regulate various mucosal functions, its role in the physiological control of the human intestinal epithelial barrier is unknown. The aim of this study was to investigate whether the ENS is able to modulate epithelial barrier permeability and a key tight junction-associated protein, zonula occludens-1 (ZO-1). Therefore, we developed a co-culture model, consisting of human submucosa containing the submucosal neuronal network and human polarized colonic epithelial monolayers (HT29-Cl.16E or Caco-2). Submucosal neurons were activated by electrical field stimulation (EFS). Permeability was assessed by measuring the flux of paracellular permeability markers (FITC-dextran or FITC-inulin) across epithelial monolayers. Expression of ZO-1 was determined by immunofluorescence, quantitative immunoblot analysis, and real time RT-PCR. Using the coculture model, we showed that EFS of submucosal neurons resulted in a reduction in FITC-dextran or FITC-inulin fluxes, which was blocked by TTX. In HT29-Cl.16E, the effect of submucosal neuron activation was blocked by a VIP receptor antagonist (VIPra) and reproduced by VIP. Furthermore, ZO-1 expression (mRNA, protein) assessed in HT29-Cl.16E, was significantly increased after submucosal neuron activation by EFS. These effects on ZO-1 expression were blocked by TTX and VIPra and reproduced by VIP. In conclusion, our results strongly suggest a modulatory role of VIPergic submucosal neuronal pathways on intestinal epithelial barrier permeability and ZO-1 expression. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/12881224/Human_ENS_regulates_the_intestinal_epithelial_barrier_permeability_and_a_tight_junction_associated_protein_ZO_1_via_VIPergic_pathways_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00066.2003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -