Altered expression of laminins in Crohn's disease small intestinal mucosa

Laminins are a large family of heterotrimeric basement membrane molecules t hat mediate crucial cell functions such as adhesion, proliferation, migrati on, and differentiation. Up to now, three distinct laminins have been ident ified in the normal human small intestinal epithelium. Laminln-1 (alpha 1 b eta 1 gamma 1) and laminin-5 (alpha 3 beta 3 gamma 2) are mainly expressed at the base of villus cells, whereas laminin-2 (alpha 2 beta 1 gamma 1) is restricted to the bottom of the crypts. The expression of these molecules h as not yet been studied in Crohn's disease (CD), but it could be altered, i n light of the important changes occurring in the architecture of the crypt villus axis under the active state of the disease. To test this hypothesis, the expression of laminin alpha 1, alpha 2, and alpha 3 subunits was analy zed in control, inflamed, and corresponding uninflamed CD small intestinal specimens by indirect immunofluorescence and reverse transcriptase-polymera se chain reaction. Surprisingly, alpha 1 and alpha 3 remained strongly expr essed by all villus cells,whereas alpha 2, normally expressed in the bottom of the crypts in control and uninflamed CD specimens, was lacking in infla med CD specimens. However, this loss of alpha 2 expression was associated w ith a significant up-regulation of both alpha 1 and alpha 5 expression in t he crypts of inflamed CD specimens. A significant up-regulation of the alph a 1 subunit was also observed in the crypts of uninflamed CD specimens. At the transcript levels, alpha 1 was found significantly higher in inflamed t han uninflamed CD specimens. Taken together, these observations identify im portant alterations in laminin expression in the small intestine with CD an d suggest that compositional changes in the epithelial basement membrane ma y play a role in this disease.