Guy R. Sander

Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins

Coeliac disease is a chronic enteropathy caused by the ingestion of wheat gliadin and other cereal prolamines derived from rye and barley. In the present work, we investigated the mechanisms underlying altered barrier function properties exerted by gliadin‐derived peptides in human Caco‐2 intestinal epithelial cells. We demonstrate that gliadin alters barrier function almost immediately by decreasing transepithelial resistance and increasing permeability to small molecules (4 kDa). Gliadin caused a reorganisation of actin filaments and altered expression of the tight junction proteins occludin, claudin‐3 and claudin‐4, the TJ‐associated protein ZO‐1 and the adherens junction protein E‐cadherin.

Expression of Notch Receptors and Ligands in the Adult Gut

The Notch signaling pathway has become recognized as a vitally important pathway in regulating proliferative/differentiative decisions and cell fate. To explore the involvement of the Notch pathway in adult gut, we investigated the expression of Notch receptors and their ligands by Northern blotting and in situ hybridization. Notch receptors and ligands were expressed in both proliferative and post-mitotic cells throughout adult rat gut, variously in epithelial, immune, and endothelial cells. Expression of Notch1, Jagged1, and Jagged2 frequently overlapped, whereas Notch2 expression was restricted to specific crypt cells, the lamina propria of the large intestine, and Peyers patch lymphocytes. We propose that the expression of multiple Notch receptors and ligands in a range of different intestinal cell types indicates that this signaling pathway underpins many of the processes involved in the maintenance and function of the adult gut.

Expression of Notch1 and Jagged2 in the Enteric Nervous System

The Notch signaling pathway is a vitally important pathway in regulating brain development. To explore the involvement of the Notch pathway in neuronal cells of adult rat gut, we investigated the expression of Notch1 and Jagged2 by in situ hybridization (ISH) and immunohistochemistry (IHC). In the enteric nervous system, Notch1 and Jagged2 were expressed in ganglia of the submucosal and myenteric plexus. Notch1 was preferentially expressed in cholinergic neurons lacking calretinin or nitric oxide synthase (NOS), whereas Jagged2 was present in most neuron subtypes. We propose that Notch1 and Jagged2 have a continuing role in the maintenance and function of neuronal cells in the adult enteric nervous system.

Expression of the Homeobox Gene Barx2 in the Gut

Barx2 is a member of the Bar class of homeobox genes and has been shown to regulate specific cell adhesion molecules, L1, Ng-CAM, N-CAM, and cadherin 6. By Northern blotting and in situ hybridization, we show that Barx2 is expressed throughout the gut and is located in epithelial cells of the proliferative and differentiative regions of the stomach, esophagus, and intestine. Barx2 was expressed in muscle cells of the muscularis externa and also showed a graded pattern of expression in intestinal enterocytes, decreasing in a crypt-to-villous direction. We speculate that Barx2 may regulate cell adhesion molecules in epithelial cells of the gut.