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 alpha 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 alpha chains in the human stomach at different ages (8-22 weeks of gestation) using indirect immunofluorescence. In the body, fundus and antrum regions, the beta1 and alpha6 subunits were associated with the entire epithelium at all developmental stages in the same way as laminin chains (alpha1/alpha5) detected with 4C7 monoclonal antibody. By contrast, the alpha3 and beta4 subunits of alpha3beta1 and alpha6beta4 integrins together with the laminin alpha3-chain were concentrated in the surface and foveolus compartments composed of differentiating mucous cells. Most importantly, the alpha2 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 (alpha2-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 alpha2 and alpha3 integrin subunits as well as the cellular re-distribution of alpha2beta1 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.

Integrin expression in developing human salivary glands

“…Our findings showed stronger and wider presence of integrins as differentiation advanced. This is also reported in the development of human gastric mucosa, in which integrins b1 and b4 are present in foveolas gland units and in gastric epithelial cells (Che´nard et al 2000).…”

“…b4 integrin was prominently deposited in the basal pole and baso-lateral portion of salivary gland structures. This re-distribution phenomenon may account for the secretory functions of salivary glands, as it has also been reported in other secretory organs such as stomach, lungs and breast (Che´nard et al 2000). According to a study on tracheal tubular morphogenesis, the cellular localisation of b1 integrin may yet be related to cell migration and tubule formation (Coraux et al 2000).…”

Identification of β integrin‐like‐ and fibronectin‐like proteins in the bivalve mollusk Mytilus trossulus

“…In vertebrates, the timed expression of β 1 integrin is essential for the development and differentiation of different types of epithelia, including the epithelium of the digestive system and, in particular, the human gastric mucosa (Chenard et al . ). In this case, the expression of integrin subunits has been shown to correlate with the maintenance of a polarized phenotype and the differentiated status of epithelial cells.…”

“…It should be noted that b integrin-LP was also detected on the cell membranes in other larval organs of the developing digestive system, with strong antibody staining seen in the large hepatopancreas cells, a portion of the intestinal tube and esophagus in M. trossulus veligers. In vertebrates, the timed expression of b1 integrin is essential for the development and differentiation of different types of epithelia, including the epithelium of the digestive system and, in particular, the human gastric mucosa (Chenard et al 2000).…”

Imunoexpressão de caderinas e integrinas no desenvolvimento do epitélio cutâneo humano

“…Na mucosa gástrica em desenvolvimento, a expressão coordenada de integrinas 2 e 3 e a re-distribuição celular da integrina 21 parece representar eventos-chave na diferenciação das glândulas secretórias, especialmente células responsáveis pela síntese e secreção de enzimas digestivas (Chénard et al, 2000).…”