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

Laminins are a large family of heterotrimeric basement membrane molecules that mediate crucial cell functions such as adhesion, proliferation, migration, and differentiation. Up to now, three distinct laminins have been identified in the normal human small intestinal epithelium. Laminln-1 (alpha 1 beta 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 has not yet been studied in Crohn's disease (CD), but it could be altered, in light of the important changes occurring in the architecture of the cryptvillus 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 analyzed in control, inflamed, and corresponding uninflamed CD small intestinal specimens by indirect immunofluorescence and reverse transcriptase-polymerase chain reaction. Surprisingly, alpha 1 and alpha 3 remained strongly expressed by all villus cells,whereas alpha 2, normally expressed in the bottom of the crypts in control and uninflamed CD specimens, was lacking in inflamed CD specimens. However, this loss of alpha 2 expression was associated with a significant up-regulation of both alpha 1 and alpha 5 expression in the crypts of inflamed CD specimens. A significant up-regulation of the alpha 1 subunit was also observed in the crypts of uninflamed CD specimens. At the transcript levels, alpha 1 was found significantly higher in inflamed than uninflamed CD specimens. Taken together, these observations identify important alterations in laminin expression in the small intestine with CD and suggest that compositional changes in the epithelial basement membrane may play a role in this disease.