Altered Expression of Laminins in Crohn's Disease Small Intestinal Mucosa

• Published in: The American journal of pathology Vol. 156; no. 1; pp. 45 - 50
• Main Authors: Bouatrouss, Yamina, Herring-Gillam, F. Elizabeth, Gosselin, Jean, Poisson, Jacques, Beaulieu, Jean-François
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 2000; American Society for Investigative Pathology
• Subjects: Adult; Biological and medical sciences; Crohn Disease - metabolism; Female; Fluorescent Antibody Technique, Indirect; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Intestinal Mucosa - metabolism; Intestine, Small - metabolism; Laminin - genetics; Laminin - metabolism; Male; Medical sciences; Other diseases. Semiology; Protein Isoforms - genetics; Protein Isoforms - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Short Communications; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tissue Distribution; Human; Immunohistochemistry; Pathogenesis; Reverse transcription; Small intestine; Inflammatory disease; Basement membrane; Polymerase chain reaction; Pathology; Crohn disease; Laminin; Digestive diseases; Intestinal disease; Molecular biology; Immunofluorescence
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)64704-9

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 (α1β1γ1) and laminin-5 (α3β3γ2) are mainly expressed at the base of villus cells, whereas laminin-2 (α2β1γ1) 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 α1, α2, and α3 subunits was analyzed in control, inflamed, and corresponding uninflamed CD small intestinal specimens by indirect immunofluorescence and reverse transcriptase-polymerase chain reaction. Surprisingly, α1 and α3 remained strongly expressed by all villus cells, whereas α2, normally expressed in the bottom of the crypts in control and uninflamed CD specimens, was lacking in inflamed CD specimens. However, this loss of α2 expression was associated with a significant up-regulation of both α1 and α3 expression in the crypts of inflamed CD specimens. A significant up-regulation of the α1 subunit was also observed in the crypts of uninflamed CD specimens. At the transcript levels, α1 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.