Abstract
In healthy gut enteric glial cells (EGC) are essential to intestinal epithelial barrier (IEB) functions. In Crohn’s Disease (CD), both EGC phenotype and IEB functions are altered, but putative involvement of EGC in CD pathogenesis remains unknown and study of human EGC are lacking. EGC isolated from CD and control patients showed similar expression of glial markers and EGC-derived soluble factors (IL6, TGF-β, proEGF, GSH) but CD EGC failed to increase IEB resistance and healing. Lipid profiling showed that CD EGC produced decreased amounts of 15-HETE, 18-HEPE, 15dPGJ2 and 11βPGF2α as compared to healthy EGC. They also had reduced expression of the L-PGDS and AKR1C3 enzymes. Produced by healthy EGC, the 11βPGF2 activated PPARγ receptor of intestinal epithelial cells to induce cell spreading and IEB wound repair. In addition to this novel healing mechanism our data show that CD EGC presented impaired ability to promote IEB functions through defect in L-PGDS-AKR1C3-11βPGF2α dependent pathway.
Highlights
In healthy gut enteric glial cells (EGC) are essential to intestinal epithelial barrier (IEB) functions
Crohn’s Disease (CD) EGC did not impact spreading (Fig. 2c,d) or transepithelial electrical resistance (TER) (Fig. 2e) as compared to Caco-2 monolayer cultured alone. These results demonstrate that EGC from CD patients have impaired effects on IEB healing
The main goal of this work was to assess whether primary cultures of EGC from CD patients have altered impact on IEB healing, compared to EGC from control patients
Summary
In healthy gut enteric glial cells (EGC) are essential to intestinal epithelial barrier (IEB) functions. Produced by healthy EGC, the 11βPGF2 activated PPARγ receptor of intestinal epithelial cells to induce cell spreading and IEB wound repair. In addition to this novel healing mechanism our data show that CD EGC presented impaired ability to promote IEB functions through defect in L-PGDS-AKR1C3-11βPGF2α dependent pathway. It has been well demonstrated that IEB functions, including intestinal healing, are regulated by neighboring cells, the so-called microenvironment, and in particular the enteric nervous system (ENS)[8]. EGC promote mucosal healing via enhanced cell spreading/restitution and pro-epidermal growth factor (proEGF) secretion[21] and decrease intestinal permeability via S-nitrosoglutathione (GSNO) production[22]
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