• What Changes Occur in the Esophageal Epithelial Barrier During Disease Development?

What Changes Occur in the Esophageal Epithelial Barrier During Disease Development?

A review article in the May issue of Clinical Gastroenterology and Hepatology discusses esophageal epithelial barrier structure and function, new and old techniques for studying this barrier, and changes that occur during development of esophageal diseases.

Stratified squamous epithelium of the esophagus with magnification of the intercellular apical junction complex, showing the proteins involved in each of the 3 components of this complex. E-cadherin, epithelial-cadherin; ZO, zonulin

To identify mechanisms of diseases associated with barrier dysfunction, such as gastroesophageal reflux disease (GERD), eosinophilic esophagitis, Barrett’s esophagus, or obesity, it is important to understand esophageal epithelial development, the microscopic anatomy of the barrier, and the structure and function change.

Christopher H. Blevins et al cover these topics in their review article, beginning with the embryonic development of the esophagus from the foregut into the eventual stratified squamous epithelium (see figure). They explain that the primary function of the developed barrier is to protect the deeper mucosal and submucosal layers from noxious intraluminal contents.

 Blevins et al review how the apical junction complex connects cells and regulates the intercellular space diameter, comprising the tight junction complex, the adherens junctions, and the desmosomes. The tight junction complex, the most apically located component of the apical junctional complex, connects cell membranes, actively regulates paracellular permeability of ions, and demarcates the boundary between basolateral and apical cell surface. The proteins in these complexes are altered in number and distribution in patients with diseases such as eosinophilic esophagitis.

The authors discuss the best methods to assess epithelial barrier structure and morphology, including light microscopy, transmission electron microscopy, and confocal laser endomicroscopy. Confocal laser endomicroscopy has been used to study the small bowel and colon in patients with inflammatory bowel diseases or irritable bowel syndrome. Blevins et al describe defects in the epithelial barrier of patients with eosinophilic esophagitis, GERD, Barrett’s esophagus, or obesity.

They conclude that although paracellular permeability contributes to many disorders of the esophagus, due to alterations in proteins that maintain the intercellular space, it is not clear how these regulatory proteins function in the normal esophagus or inflammation leads to their dysfunction.

However, use of different microscopy methods and immunohistochemical techniques to determine the composition of the adherens junction complex and studies to correlate these changes with clinical findings and measurements of paracellular permeability could help us better understand the function of esophageal mucosal barrier and lead to new treatments for diseases.

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