Differential expression of the VLA family of integrins along the crypt-villus axis in the human small intestine

Abstract

Regulation of epithelial cell proliferation, migration and differentiation under physiological conditions remains poorly understood. Interaction of the cells with their underlying basement membrane through integrins, a specific subset of cell surface binding proteins, is one potential mechanism. In the present work, I examined this hypothesis by investigating the distribution of a variety of epithelial basement membrane proteins and the expression of the members of the VLA family of integrins in the adult intestinal epithelium. Indeed, this rapidly renewing simple epithelium contains within its functional unit, the crypt-villus axis, essentially two distinct cell populations: the proliferative and undifferentiated crypt cells and the mature enterocytes on the villus. Although immunolocalization of basement membrane molecules revealed that laminin, type IV collagen and heparan sulfate proteoglycan are distributed homogeneously all along the crypt-villus axis, other non-exclusive basement membrane components were found differentially expressed. Tenascin was concentrated at the base of both villus and lower crypt cells while cellular fibronectin was mostly detected in association with the crypt cells. Moreover, VLA beta 1 as well as 5 of the 6 VLA alpha subunits tested were expressed by intestinal epithelial cells under specific patterns of staining. The beta 1 and alpha 6 subunits were strongly detected at the base of all enterocytes while alpha 5, also detected all along the crypt-villus axis, was weaker and consistently appeared with a punctated/interrupted pattern. On the other hand, the VLA alpha 1, alpha 2 and alpha 3 were expressed at the basolateral domains of enterocytes under distinctive crypt-villus gradients. The alpha 1 subunit was detected at the base of all epithelial cells but lateral staining was only observed in differentiating cells (middle and upper crypt). Finally, in most specimens, alpha 2 and alpha 3 displayed strictly complementary staining patterns for the lower crypt region (alpha 2+, alpha 3-) and the upper crypt-to-villus region (alpha 2-, alpha 3+). Taken together, these data emphasize that proliferation, migration and differentiation in the normal state are susceptible to various influences including compositional changes in the basement membrane and differential expression of receptors for these components.