MESENCHYMAL REGULATION OF DIFFERENTIATION OF INTESTINAL EPITHELIAL-CELLS

Intestinal epithelial differentiation requires the presence of mesench yme, but the exact nature of this epithelial-mesenchymal interaction i s unknown. The role of humoral and extracellular matrix factors in det ermining intestinal epithelial differentiation was examined by exposin g a nontransformed, immature, rat small-intestinal cell line (IEC-6) t o intestinal fibroblast-conditioned media or by growing the cells on m atrix deposited by intestinal fibroblasts. Differentiation was assesse d morphologically and by induction of the disaccharidase sucrase, whic h is a marker of intestinal epithelial maturation. When exposed to fet al intestinal fibroblast-conditioned medium or grown on extracellular matrix prepared from fetal intestinal fibroblasts, IEC-6 cells showed a significant increase in sucrase activity. The addition of cortisol t o IEC-6 cells cultured on intestinal matrix also led to increased sucr ase expression, as measured by enzyme activity and protein and messeng er RNA levels. Ultrastructurally, cells cultured on intestinal fibrobl ast matrix in the presence of cortisol displayed a more differentiated phenotype. In contrast, there was no induction of sucrase activity in cells exposed to lung-conditioned media or grown on lung fibroblast m atrix. These studies suggest that both humoral and matrix factors from intestinal mesenchyme are involved in intestinal epithelial different iation and that these factors appear to be organ specific.