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Article Dans Une Revue Scientific Reports Année : 2019

Characterisation of proguanylin expressing cells in the intestine – evidence for constitutive luminal secretion

Stephen J Middleton
  • Fonction : Auteur
Richard H Hardwick
  • Fonction : Auteur
Jennifer L Percival-Alwyn
  • Fonction : Auteur
Tris Vaughan
  • Fonction : Auteur
Franco Ferraro
  • Fonction : Auteur
Benjamin G Challis
  • Fonction : Auteur
Maria Groves
  • Fonction : Auteur

Résumé

Abstract Guanylin, a peptide implicated in regulation of intestinal fluid secretion, is expressed in the mucosa, but the exact cellular origin remains controversial. In a new transgenic mouse model fluorescent reporter protein expression driven by the proguanylin promoter was observed throughout the small intestine and colon in goblet and Paneth(-like) cells and, except in duodenum, in mature enterocytes. In Ussing chamber experiments employing both human and mouse intestinal tissue, proguanylin was released predominantly in the luminal direction. Measurements of proguanylin expression and secretion in cell lines and organoids indicated that secretion is largely constitutive and requires ER to Golgi transport but was not acutely regulated by salt or other stimuli. Using a newly-developed proguanylin assay, we found plasma levels to be raised in humans after total gastrectomy or intestinal transplantation, but largely unresponsive to nutrient ingestion. By LC-MS/MS we identified processed forms in tissue and luminal extracts, but in plasma we only detected full-length proguanylin. Our transgenic approach provides information about the cellular origins of proguanylin, complementing previous immunohistochemical and in-situ hybridisation results. The identification of processed forms of proguanylin in the intestinal lumen but not in plasma supports the notion that the primary site of action is the gut itself.
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hal-03208847 , version 1 (26-04-2021)

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Florent Serge Dye, Pierre Larraufie, Richard Kay, Tamana Darwish, Juraj Rievaj, et al.. Characterisation of proguanylin expressing cells in the intestine – evidence for constitutive luminal secretion. Scientific Reports, 2019, 9 (1), ⟨10.1038/s41598-019-52049-0⟩. ⟨hal-03208847⟩
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