Loss of Sonic Hedgehog Leads to Alterations in Intestinal Secretory Cell Maturation and Autophagy

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jun 3

PMID 24887421

Citations 16

Authors

Jessica Gagne-Sansfacon

Joannie M Allaire

Christine Jones

Francois Boudreau

Nathalie Perreault

Affiliations

Soon will be listed here.

Abstract

Background: Intestinal epithelial cells express the Sonic and Indian hedgehog ligands. Despite the strong interest in gut hedgehog signaling in GI diseases, no studies have specifically addressed the singular role of intestinal epithelial cell Sonic hedgehog signaling. The aim of this study was to investigate the specific role of Sonic hedgehog in adult ileal epithelial homeostasis.

Methodology/principal Findings: A Sonic hedgehog intestinal epithelial conditional knockout mouse model was generated. Assessment of ileal histological abnormalities, crypt epithelial cell proliferation, epithelial cell fate, junctional proteins, signaling pathways, as well as ultrastructural analysis of intracellular organelles were performed in control and mutant mice. Mice lacking intestinal epithelial Sonic Hedgehog displayed decreased ileal crypt/villus length, decreased crypt proliferation as well as a decrease in the number of ileal mucin-secreting goblet cells and antimicrobial peptide-secreting Paneth cells during adult life. These secretory cells also exhibited disruption of their secretory products in mutant mice. Ultrastructural microscopy analysis revealed a dilated ER lumen in secretory cells. This phenotype was also associated with a decrease in autophagy.

Conclusions/significance: Altogether, these findings indicate that the loss of Sonic hedgehog can lead to ileal secretory cell modifications indicative of endoplasmic reticulum stress, accompanied by a significant reduction in autophagy.

Citing Articles

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Yang X, Sun W, Jing X, Zhang Q, Huang H, Xu Z Respir Res. 2022; 23(1):86.

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Yin W, Liontos A, Koepke J, Ghoul M, Mazzocchi L, Liu X Development. 2022; 149(3).

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Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling.

Nicolas V, Allaire J, Alfonso A, Pupo Gomez D, Pomerleau V, Giroux V Cells. 2021; 10(11).

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