The Enteric Glia: Identity and Functions

Coelho-Aguiar, Juliana de Mattos; Bon-Frauches, Ana Carina; Tavares-Gomes, Ana Lúcia; Veríssimo, Carla Pires; Aguiar, Diego Pinheiro; Matias, Diana; Thomasi, Beatriz Bastos de Moraes; Gomes, Antoniella S.; Brito, Gerly Anne de Castro; Moura‐Neto, Vivaldo

doi:10.1002/glia.22795

Cited by 91 publications

(70 citation statements)

References 160 publications

(197 reference statements)

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“…3C). Enteric glial cells originate from the neural crest’, consistent with their presence in the lamina propria and submucosa of the gut 26 . Cultures from untreated WT mice isolated using the same protocol were also enriched in glial cells (Gfap + , S100b + , Sox10 + ) but were negative for gastrin (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 83%

Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells

et al. 2017

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Background The Multiple Endocrine Neoplasia, type 1 (MEN1) locus encodes the nuclear tumor suppressor protein menin. MEN1 mutations frequently cause neuroendocrine tumors (NETs) such as gastrinomas, remarkable for their predominant duodenal location and local metastasis at the time of diagnosis. Diffuse gastrin cell hyperplasia precedes the appearance of MEN1 gastrinomas, which develop within submucosal Brunner’s glands. We show here that loss of menin in enteric glial cells induces gastrin expression. Aim To determine how menin regulates gastrin gene expression and induces the generation of submucosal gastrin-expressing cell hyperplasia. Methods Primary enteric glial cultures were generated from the Villin-Cre:Men1FL/FL:Sst−/− mice with or without inhibition of gastric acid using omeprazole. In addition, primary enteric glial cells from wild type mice were treated with gastrin and were separated into nuclear and cytoplasmic fractions. Forskolin and H89 treatments were used to activate or inhibit protein kinase A activity. Immunoprecipitation with menin or ubiquitin was used to demonstrate posttranslational modification of menin. Primary glial cells were treated with Leptomycin b and MG132 to block nuclear export and proteasome activity, respectively. Results Gfap+ enteric glial cells expressed gastrin de novo through a feedforward PKA-dependent mechanism. Gastrin-induced nuclear export of menin through Cckbr-mediated PKA activation. Once exported menin was ubiquitinated and degraded by the proteasome. Gfap and other enteric glial markers co-localized with gastrin in human duodenal gastrinomas. Conclusion Collectively, these results suggest that MEN1-associated gastrinomas, which develop in the submucosa might arise from enteric glial cells through hormone-dependent PKA signaling that abrogates menin function leading to hypergastrinemia and associated sequelae.

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Section: Resultsmentioning

confidence: 83%

Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells

et al. 2017

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“…GFAP, the major protein constituent of glial intermediate filaments in the differentiated fibrous and protoplasmic astrocytes of the central nervous system, is involved in controlling the shape and the movement of these cells [41, 42]. Increased expression of GFAP and S100β represents astroglial activation and gliosis [41, 43].…”

Section: Resultsmentioning

confidence: 99%

The involvement of mast cells in the irinotecan-induced enteric neurons loss and reactive gliosis

Nogueira

Costa

Gomes

et al. 2017

J Neuroinflammation

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BackgroundThe irinotecan (CPT-11) causes intestinal mucositis and diarrhea that may be related to changes in the enteric nervous system (ENS). In inflammatory condition, mast cells release a variety of pro-inflammatory mediators that can interact with the ENS cells. It has not been explored whether CPT-11 is able to alter the enteric glial and neuronal cell, and the role of mast cells in this effect. Therefore, this study was conducted to investigate the effect of CPT-11 on the enteric glial and neuronal cells, as well as to study the role of mast cells in the CPT-11-induced intestinal mucositis.MethodsIntestinal mucositis was induced in Swiss mice by the injection of CPT-11 (60 mg/kg, i.p.) once a day for 4 days following by euthanasia on the fifth day. To investigate the role of mast cells, the mice were pretreated with compound 48/80 for 4 days (first day, 0.6 mg/kg; second day, 1.0 mg/kg; third day, 1.2 mg/kg; fourth day, 2.4 mg/kg) to induce mast cell degranulation before the CPT-11 treatment.ResultsHere, we show that CPT-11 increased glial fibrillary acidic protein (GFAP) and S100β gene and S100β protein expressions and decreased HuC/D protein expression in the small intestine segments. Concomitantly, CPT-11 enhanced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and inducible nitric oxide synthase (iNOS) gene expression, associated with an increase in the total number macrophages (positive cells for ionized calcium-binding adapter molecule, Iba-1) and degranulated mast cells in the small intestine segments and caused significant weight loss. The pretreatment with compound 48/80, an inductor of mast cells degranulation, significantly prevented these CPT-11-induced effects.ConclusionsOur data suggests the participation of mast cells on the CPT-11-induced intestinal mucositis, macrophages activation, enteric reactive gliosis, and neuron loss.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0854-1) contains supplementary material, which is available to authorized users.

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“…In addition, transcription factors -especially Sox10 and Pax3 -and Hdac1/2 histone deacetylases, which regulate chromatin remodeling, work in concert to promote the formation of Schwann cell precursors from neural crest cells (Jacob, 2015). Neural crest cells also give rise to enteric glial cells in the gastrointestinal tract (Coelho-Aguiar et al, 2015) and olfactory ensheathing cells that reside in both the PNS and the olfactory bulb in the CNS (Barraud et al, 2010). The functions of these and their precise mechanisms of specification are still being worked out, and it will be interesting to determine similarities and differences compared with Schwann cell precursors.…”

Section: Origins and Specification Of Gliamentioning

confidence: 99%

Glia in mammalian development and disease

2015

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Glia account for more than half of the cells in the mammalian nervous system, and the past few decades have witnessed a flood of studies that detail novel functions for glia in nervous system development, plasticity and disease. Here, and in the accompanying poster, we review the origins of glia and discuss their diverse roles during development, in the adult nervous system and in the context of disease.

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The Enteric Glia: Identity and Functions

Cited by 91 publications

References 160 publications

Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells

Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells

The involvement of mast cells in the irinotecan-induced enteric neurons loss and reactive gliosis

Glia in mammalian development and disease

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