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Related Concept Videos

Regulation of the Digestive System01:25

Regulation of the Digestive System

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Digestive activity regulation hinges on three primary components. Activation is prompted by a multitude of mechanical and chemical indicators, primarily detected by receptors within the stomach and intestines' walls. These receptors predominantly respond to factors such as mechanical stretching of the organ walls, changes in pH and osmolarity, and the presence of digesting materials and their by-products.
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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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The gastrointestinal tract, responsible for the digestion and absorption of nutrients, is safeguarded by the intestinal barrier, which consists of secretory, physical, and immune components. At the forefront is the secretory barrier, composed of essential elements such as mucus, gut microbiota, and defense proteins. They collaborate to break down food particles, facilitate nutrient absorption, and maintain optimal gut health. These secretory components ensure the smooth functioning of the...
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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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The small intestine exhibits a unique histological structure that significantly enhances its function in digestion and nutrient absorption. These structures include circular folds, villi, and various specialized cells that collectively facilitate the digestion of food.
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Related Experiment Video

Updated: May 21, 2025

In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
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Enteroendocrine cells regulate intestinal barrier permeability.

Jennifer G Nwako1, Sparsh D Patel1, Taevon J Roach1

  • 1Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States.

American Journal of Physiology. Cell Physiology
|March 17, 2025
PubMed
Summary

Enteroendocrine cells are crucial for maintaining a healthy intestinal barrier. Supplementing with peptide YY and somatostatin can rescue barrier defects, offering potential new therapies for gastrointestinal diseases.

Keywords:
barrier functionenteroendocrine cellsintestinal organoidspeptide YYtight junctions

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Area of Science:

  • Gastroenterology and immunology
  • Epithelial biology
  • Cellular and molecular medicine

Background:

  • The intestinal epithelial barrier, maintained by tight junctions, is vital for nutrient absorption and pathogen defense.
  • Barrier dysfunction, driven by inflammation, is a hallmark of inflammatory bowel disease (IBD).
  • Current therapeutic strategies do not directly enhance intestinal epithelial barrier function.

Purpose of the Study:

  • To investigate the role of enteroendocrine cells in maintaining intestinal epithelial barrier integrity.
  • To determine if enteroendocrine cells and their secreted hormones can restore barrier function in disease models.

Main Methods:

  • Utilized human intestinal enteroids with genetic deletion of enteroendocrine cells cultured on Transwell filters.
  • Assessed barrier function by measuring transepithelial electrical resistance and paracellular permeability.
  • Evaluated the localization and abundance of key junctional proteins (zona occludens 1, occludin, claudin-2).
  • Tested the effects of peptide tyrosine-tyrosine (PYY) and octreotide supplementation on barrier function.

Main Results:

  • Enteroendocrine cells are essential for maintaining barrier integrity in both stem and differentiated intestinal cultures.
  • Supplementation with PYY and octreotide rescued barrier defects in enteroendocrine-deficient cultures, even with inflammatory cytokine exposure (tumor necrosis factor).
  • Improvements in barrier function occurred independently of significant changes in the abundance of major tight junction proteins.

Conclusions:

  • Enteroendocrine cells play a critical, previously unappreciated role in augmenting intestinal epithelial barrier function, particularly during inflammation.
  • Secreted hormones from enteroendocrine cells, such as PYY and somatostatin, can effectively restore barrier integrity.
  • These findings present a novel therapeutic avenue for strengthening the intestinal barrier in IBD and other gastrointestinal disorders.