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Glioplasticity in irritable bowel syndrome

Abstract : Background: growing evidence indicates a wide array of cellular remodeling in the mucosal microenvironment during irritable bowel syndrome (IBS), which possibly contributes to pathophysiology and symptom generation. Here, we investigated whether enteric glial cells (EGC) may be altered, and which factors/mechanisms lead to these changes. Methods: Colonic mucosal biopsies of IBS patients (13 IBS‐Constipation [IBS‐C]; 10 IBS‐Diarrhea [IBS‐D]; 11 IBS‐Mixed [IBS‐M]) and 24 healthy controls (HC) were analyzed. Expression of S100β and GFAP was measured. Cultured rat EGC were incubated with supernatants from mucosal biopsies, then proliferation and Ca2+ response to ATP were analyzed using flow cytometry and Ca2+ imaging. Histamine and histamine 1‐receptor (H1R) involvement in the effects of supernatant upon EGC was analyzed. Key Results: Compared to HC, the mucosal area immunoreactive for S100β was significantly reduced in biopsies of IBS patients, independently of the IBS subtype. IBS‐C supernatants reduced EGC proliferation and IBS‐D and IBS‐M supernatants reduced Ca2+ response to ATP in EGC. EGC expressed H1R and the effects of supernatant upon Ca2+ response to ATP in EGC were blocked by pyrilamine and reproduced by histamine via H1R. IBS supernatants reduced mRNA expression of connexin‐43. The S100β‐stained area was negatively correlated with the frequency and intensity of pain and bloating. Conclusion and Inferences: Changes in EGC occur in IBS, involving mucosal soluble factors. Histamine, via activation of H1R‐dependent pathways, partly mediates altered Ca2+ response to ATP in EGC. These changes may contribute to the pathophysiology and the perception of pain and bloating in patients with IBS.
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https://hal-cnrs.archives-ouvertes.fr/hal-03153591
Contributor : Malvyne Rolli-Derkinderen <>
Submitted on : Tuesday, March 9, 2021 - 1:54:40 PM
Last modification on : Tuesday, July 6, 2021 - 5:18:02 PM
Long-term archiving on: : Thursday, June 10, 2021 - 6:05:40 PM

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N. Lilli, L. Quénéhervé, S. Haddara, C. Brochard, P. Aubert, et al.. Glioplasticity in irritable bowel syndrome. Neurogastroenterology & Motility, Wiley, 2018, 30 (4), pp.e13232. ⟨10.1111/nmo.13232⟩. ⟨hal-03153591⟩

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