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From the Département d’anatomie et de biologie
cellulaire,*
Medical Research Council Group in Functional
Development and Physiopathology of the Digestive Tract; the
Département de pathologie,
and
the Département de chirurgie,
Faculté de médecine, Université de Sherbrooke,
Sherbrooke, Quebec, Canada
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. Laminin-1 (
1ß1
1) and
laminin-5 (3ß32) are mainly expressed at the base of villus
cells, whereas laminin-2 (2ß11) 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 crypt-villus axis under the active state of the
disease. To test this hypothesis, the expression of laminin
1, 2, and 3 subunits was analyzed in
control, inflamed, and corresponding uninflamed CD
small intestinal specimens by indirect immunofluorescence and reverse
transcriptase-polymerase chain reaction. Surprisingly, 1 and
3 remained strongly expressed by all villus cells, whereas
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 2 expression was associated
with a significant up-regulation of both 1 and 3 expression in
the crypts of inflamed CD specimens. A significant up-regulation of the
1 subunit was also observed in the crypts of uninflamed CD
specimens. At the transcript levels, 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.
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