Defects in 15-HETE Production and Control of Epithelial Permeability by Human Enteric Glial Cells From Patients With Crohn’s Disease

Pochard, Camille; Coquenlorge, Sabrina; Jaulin, Julie; Cenac, Nicolas; Vergnolle, Nathalie; Meurette, G.; Freyssinet, Marie; Neunlist, Michel; Rolli–Derkinderen, Malvyne

doi:10.1053/j.gastro.2015.09.038

Cited by 68 publications

(75 citation statements)

References 63 publications

(73 reference statements)

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“…Surprisingly, in this latter setting, there were no changes in S100β and GFAP expression in inflamed areas vs controls . This finding is in line with our previous data showing no changes in S100β or GFAP expression in EGC isolated from Crohn's disease tissues, although arachidonic acid metabolites were reduced in vitro . Taken together, these results suggest that EGC could display an altered functional response in IBS regardless of an apparently normal expression of S100β and GFAP.…”

Section: Discussionsupporting

confidence: 90%

Glioplasticity in irritable bowel syndrome

Lilli

Quénéhervé

Haddara

et al. 2017

Neurogastroenterology Motil

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Section: Discussionsupporting

confidence: 90%

Glioplasticity in irritable bowel syndrome

Lilli

Quénéhervé

Haddara

et al. 2017

Neurogastroenterology Motil

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“…Enteric glia can secrete a number of signaling molecules that modulate epithelial function in vitro 8, 10, 32–36 yet glia seem unnecessary for epithelial integrity in vivo . This difference could occur because other cell types secrete these signaling molecules in the absence of glia, or because enteric glia have different capabilities in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Enteric Glia Regulate Gastrointestinal Motility but Are Not Required for Maintenance of the Epithelium in Mice

et al. 2017

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Background & Aims When the glial fibrillary acidic protein (GFAP) promoter is used to express cellular toxins that eliminate glia in mice, intestinal epithelial permeability and proliferation increase; this led to the concept that glia are required for maintenance of the gastrointestinal epithelium. Many enteric glia, however, particularly in the mucosa, do not express GFAP. In contrast, virtually all enteric glia express proteolipid protein 1 (PLP1). We investigated whether elimination of PLP1-expressing cells compromises epithelial maintenance or gastrointestinal motility. Methods We generated mice that express tamoxifen-inducible Cre recombinase under control of the Plp1 promoter and carry the diptheria toxin subunit A (DTA) transgene in the Rosa26 locus (Plp1CreER;Rosa26DTA mice). In these mice, PLP1-expressing glia are selectively eliminated without affecting neighboring cells. We measured epithelial barrier function and gastrointestinal motility in these mice and littermate controls, and analyzed epithelial cell proliferation and ultrastructure from their intestinal tissues. To compare our findings with those from previous studies, we also eliminated glia with ganciclovir in GfapHSV-TK mice. Results Expression of DTA in PLP1-expressing cells selectively eliminated enteric glia from the small and large intestines, but caused no defects in epithelial proliferation, barrier integrity, or ultrastructure. In contrast, administration of ganciclovir to GfapHSV-TK mice eliminated fewer glia but caused considerable non-glial toxicity and epithelial cell death. Elimination of PLP1-expressing cells did not reduce survival of neurons in the intestine, but altered gastrointestinal motility in female, but not male, mice. Conclusions Using the Plp1 promoter to selectively eliminate glia in mice, we found that enteric glia are not required for maintenance of the intestinal epithelium but are required for regulation of intestinal motility in females. Previous observations supporting the concept that maintenance of the intestinal epithelium requires enteric glia can be attributed to non-glial toxicity in GfapHSV-TK mice and epithelial-cell expression of GFAP. Contrary to widespread notions, enteric glia are therefore not required for epithelial homeostasis. However, they regulate intestinal motility in a sex-dependent manner.

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“…In addition to provide regulatory signals for the development and function of neurons, [42][43][44] EGCs regulate the intestinal epithelial barrier. 45,46 Depletion of EGCs leads to increased paracellular permeability, 47,48 and disruption of the EGCs network leads to enhanced mucosal permeability, which is thought to be an important etiology of intestinal inflammation of CD, 44 suggesting EGCs play an important role in maintaining intestinal epithelial barrier. The number of EGCs was significantly greater in CD patients compared with controls 23 ; however, a reduced number of EGCs have been found in non-inflamed gut specimens of patients with CD.…”

Section: Discussionmentioning

confidence: 99%

Increased enteric glial cells in proximal margin of resection is associated with postoperative recurrence of Crohn's disease

Zhu

et al. 2018

J of Gastro and Hepatol

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Defects in 15-HETE Production and Control of Epithelial Permeability by Human Enteric Glial Cells From Patients With Crohn’s Disease

Abstract: Enteric glial cells from patients with CD have reduced production of 15-HETE, which controls IEB permeability by inhibiting adenosine monophosphate-activated protein kinase and increasing expression of zonula occludens-1.

Cited by 68 publications

References 63 publications

Glioplasticity in irritable bowel syndrome

Glioplasticity in irritable bowel syndrome

Enteric Glia Regulate Gastrointestinal Motility but Are Not Required for Maintenance of the Epithelium in Mice

Increased enteric glial cells in proximal margin of resection is associated with postoperative recurrence of Crohn's disease

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