Transforming growth factor alpha regulation of two zinc finger-containing immediate early response genes in intestine

The epithelium lining the intestine undergoes rapid and continuous renewal. Growth factors play a role in intestinal epithelial growth regulation in vitro and in vivo. In this study, transforming growth factor alpha (TGF alpha) is shown to act as a mitogen and induce the expression of two zinc finger-containing immediate early genes [Zif268 (zinc finger protein 268) and Nup475 (nuclear protein 475)] in rat intestinal epithelial (RIE-1) cells in culture. These two gene products were initially isolated from serum-treated fibroblasts and represent growth-stimulated transcription factors. In TGF alpha-treated RIE-1 cells, nuclear run-on experiments demonstrate that TGF alpha induction of these two genes is regulated predominantly at the level of gene transcription. Utilizing in situ hybridization techniques, we show that systemic administration of TGF alpha induces expression of these two genes in the rat intestine. The predominant expression of zif268 is observed in the proliferative crypt compartment, whereas nup475 expression is concentrated in the postmitotic luminal compartment. These studies demonstrate that two immediate early genes, Nup475 and Zif268, are induced in intestinal epithelium in vitro and in vivo and thus may play a role in intestinal epithelial growth and/or differentiation.