We have previously shown that transforming growth factor-beta1 (TGF-beta1) is involved in the fibroblast-induced organization and differentiation of transformed phenotypically crypt-like T84 intestinal epithelial cells into absorptive enterocyte-like cells, when cultured within a three-dimensional collagen gel. We have used differential display polymerase chain reaction to find genes that are either up- or downregulated by TGF-beta in the T84 cells cultured in three-dimensional collagen gel and then studied how these in vitro differentially expressed genes are expressed in vivo in the small intestinal crypt-villus axis. We found that the TGF-beta1-treated T84 cells, like the villus tip enterocytes, expressed increased levels of CC3/TIP30 when compared to the undifferentiated cells. Furthermore, the expression of rab11 showed the opposite pattern, being higher in the undifferentiated cells both in vivo and in vitro. We conclude that the three-dimensional cell culture model where TGF-beta induces organization and differentiation of secretory T84 epithelial cells makes it possible to find up- and downregulated transcripts that also play a role in the human small intestinal crypt-villus axis.

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