Open Access Research article

Regulation of intestinal epithelial cells transcriptome by enteric glial cells: impact on intestinal epithelial barrier functions

Laurianne Van Landeghem123, Maxime M Mahé123, Raluca Teusan24, Jean Léger24, Isabelle Guisle24, Rémi Houlgatte245 and Michel Neunlist123*

Author Affiliations

1 INSERM, U913, Nantes, F-44000 France

2 Université de Nantes, Faculté de Médecine, Nantes, F-44000 France

3 CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, F-44000 France

4 INSERM, U915, Institut du Thorax, Nantes, F-44000 France

5 CHU Nantes, Institut du Thorax, Nantes, F-44000 France

For all author emails, please log on.

BMC Genomics 2009, 10:507  doi:10.1186/1471-2164-10-507

Published: 2 November 2009

Abstract

Background

Emerging evidences suggest that enteric glial cells (EGC), a major constituent of the enteric nervous system (ENS), are key regulators of intestinal epithelial barrier (IEB) functions. Indeed EGC inhibit intestinal epithelial cells (IEC) proliferation and increase IEB paracellular permeability. However, the role of EGC on other important barrier functions and the signalling pathways involved in their effects are currently unknown. To achieve this goal, we aimed at identifying the impact of EGC upon IEC transcriptome by performing microarray studies.

Results

EGC induced significant changes in gene expression profiling of proliferating IEC after 24 hours of co-culture. 116 genes were identified as differentially expressed (70 up-regulated and 46 down-regulated) in IEC cultured with EGC compared to IEC cultured alone. By performing functional analysis of the 116 identified genes using Ingenuity Pathway Analysis, we showed that EGC induced a significant regulation of genes favoring both cell-to-cell and cell-to-matrix adhesion as well as cell differentiation. Consistently, functional studies showed that EGC induced a significant increase in cell adhesion. EGC also regulated genes involved in cell motility towards an enhancement of cell motility. In addition, EGC profoundly modulated expression of genes involved in cell proliferation and cell survival, although no clear functional trend could be identified. Finally, important genes involved in lipid and protein metabolism of epithelial cells were shown to be differentially regulated by EGC.

Conclusion

This study reinforces the emerging concept that EGC have major protective effects upon the IEB. EGC have a profound impact upon IEC transcriptome and induce a shift in IEC phenotype towards increased cell adhesion and cell differentiation. This concept needs to be further validated under both physiological and pathophysiological conditions.