Expression of integrin subunits correlates with differentiation of epithelial cell lineages in developing human gastric mucosa

Abstract 

Laminins may play important roles in gastric gland development due to the differential localization of their α chains in human fetal fundic (oxyntic) mucosa. To extend this hypothesis, the current investigation was undertaken to compare the anatomical and cellular distribution of epithelial integrin subunits with those of laminin α chains in the human stomach at different ages (8–22 weeks of gestation) using indirect immunofluorescence. In the body, fundus and antrum regions, the β1 and α6 subunits were associated with the entire epithelium at all developmental stages in the same way as laminin chains (α1/α5) detected with 4C7 monoclonal antibody. By contrast, the α3 and β4 subunits of α3β1 and α6β4 integrins together with the laminin α3-chain were concentrated in the surface and foveolus compartments composed of differentiating mucous cells. Most importantly, the α2 integrin subunit was expressed in a rather complex pattern: (1) it was located at the base and at cell-cell boundaries of surface/foveolar epithelium, (2) was specifically repressed in differentiating parietal cells, and (3) its expression increased in maturing glands, where it became concentrated at the basal pole of epithelial cells simultaneously exhibiting a strong reactivity for laminin-2 (α2-chain). Taken altogether, our observations provide new evidence for the implication of different laminins and their receptors in the development of all human gastric epithelial lineages, surface mucous cells or glandular cells. The coordinated expression of α2 and α3 integrin subunits as well as the cellular re-distribution of α2β1 integrin likely represent key events for the differentiation of glandular secretory cell types, especially maturing chief cells responsible for the synthesis/secretion of gastric digestive enzymes in fundic-type glands.