HOME
Return to Table of Contents
IDENTIFICATION OF COLLAGEN VI AS A NEW COMPONENT OF THE BASEMENT MEMBRANE IN THE HUMAN INTESTINE
JF Groulx, D Martel, E Herring, JF Beaulieu
Équipe IRSC sur l’épithélium digestif Département d’anatomie et de biologie cellulaire, Université de Sherbrooke, Sherbrooke, Québec
INTRODUCTION: The extracellular matrix is involved in several cellular functions including cell migration, proliferation, differentiation and apoptosis. Epithelial cells interact with a thin, flexible specialized protein layer called the basement membrane (BM) which is composed of specific macromolecules including type IV collagen and laminin. The collagen VI is a unique form of heterotrimer composed by the assembly of three chains alpha1, alpha2 and alpha3 and its expression is ubiquitous in interstitial matrixes. However, until now, type VI collagen has not been considered to be part of the BM of epithelial cells.
OBJECTIVE: To study the localization and deposition of type VI collagen in the human small intestine and to study its function in human epithelial intestinal cells.
RESULTS: Immunofluorescence of cryosections of the fetal and adult small intestine shows a strong presence of type VI collagen in the interstitial matrix and, more surprising, at the base of the epithelium along the crypt-villus axis. Immunolocalization by electron microscopy established that type VI collagen was present in the BM of epithelial cells as well as in the pars fibroreticularis and the interstitial matrix. In vitro experiments have shown that both epithelial HIEC and mesenchymal HIM intestinal cell lines can produce and deposit mature type VI collagen. However, RT-PCR analysis showed that the mesenchyme is its principal source in the intact tissue. To study the role of type VI collagen, its expression in HIEC cells was shut down by using shRNA directed against the alpha1(VI) chain transcript. Preliminary results showed a deficiency in the attachment of the cells resulting in anoïkis.
CONCLUSION: Type VI collagen is a constituent of the BM of the intestinal epithelium and is produced by both the epithelial and the mesenchymal cells. It appears to be crucial for intestinal crypt cell attachment and survival.