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

Laminins may play important roles in gastric gland development due to the d ifferential localization of their alpha chains in human fetal fundic (oxynt ic) mucosa. To extend this hypothesis, the current investigation was undert aken to compare the anatomical and cellular distribution of epithelial inte grin subunits with those of laminin alpha chains in the human stomach at di fferent ages (8-22 weeks of gestation) using indirect immunofluorescence. I n the body, fundus and antrum regions, the beta 1 and alpha 6 subunits were associated with the entire epithelium at all developmental stages in the s ame way as laminin chains (alpha 1/alpha 5) detected with 4C7 monoclonal an tibody. By contrast, the alpha 3 and beta 4 subunits of alpha 3 beta 1 and alpha 6 beta 4 integrins together with the laminin alpha 3-chain were conce ntrated in the surface and foveolus compartments composed of differentiatin g mucous cells. Most importantly, the alpha 2 integrin subunit was expresse d in a rather complex pattern: (1) it was located at the base and at cell-c ell boundaries of surface/foveolar epithelium, (2) was specifically repress ed in differentiating parietal cells, and (3) its expression increased in m aturing glands, where it became concentrated at the basal pole of epithelia l cells simultaneously exhibiting a strong reactivity for laminin-2 (alpha 2-chain). Taken altogether, our observations provide new evidence for the i mplication of different laminins and their receptors in the development of all human gastric epithelial lineages, surface mucous cells or glandular ce lls. The coordinated expression of alpha 2 and alpha 3 integrin subunits as well as the cellular re-distribution of alpha 2 beta 1 integrin likely rep resent key events for the differentiation of glandular secretory cell types , especially maturing chief cells responsible for the synthesis/secretion o f gastric digestive enzymes in fundic-type glands.