TRANSFORMING GROWTH-FACTOR-ALPHA REGULATION OF 2 ZINC-FINGER-CONTAINING IMMEDIATE-EARLY RESPONSE GENES IN INTESTINE

The epithelium lining the intestine undergoes rapid and continuous ren ewal. Growth factors play a role in intestinal epithelial growth regul ation in vitro and in vivo. In this study, transforming growth factor alpha (TCF alpha) is shown to act as a mitogen and induce the expressi on of two zinc finger-containing immediate early genes [Zif268 (zinc f inger protein 268) and Nup475 (nuclear protein 475)] in rat intestinal epithelial (RIE-1) cells in culture. These two gene products were ini tially isolated from serum-treated fibroblasts and represent growth-st imulated transcription factors. In TGF alpha-treated RIE-1 cells, nucl ear run-on experiments demonstrate that TGF alpha induction of these t wo genes is regulated predominantly at the level of gene transcription . Utilizing in situ hybridization techniques, we show that systemic ad ministration of TGF alpha induces expression of these two genes in the rat intestine. The predominant expression of zif268 is observed in th e proliferative crypt compartment, whereas nup475 expression is concen trated in the postmitotic luminal compartment. These studies demonstra te that two immediate early genes, Nup475 and Zif268, are induced in i ntestinal epithelium in vitro and in vivo and thus may play a role in intestinal epithelial growth and/or differentiation.