EXPRESSION OF HOMEOBOX GENES IN A PROXIMAL TUBULAR CELL-LINE DERIVED FROM ADULT MICE

We have been studying the expression of several homeobox genes in cultures of proximal tubular epithelium (MCT cells) harvested from adult mus musculus. Hox genes 2.1, 2.3, and 3.3, in particular, are all expressed at low levels in resting MCT cells. The expression of Hox 2.1 and 3.3 were not influenced by mitogenic (epidermal growth factor; EGF, and platelet-derived growth factor; PDGF) nor by hypertrophogenic cytokines (angiotensin II; Ang II) in serum-free media. Transcripts for Hox 2.3, however, were elevated in MCT cells by Ang II, EGF, and serum treatment, as early as 30 minutes after their addition, whereas no change, or slight reductions were observed with transforming growth factor beta (TGF-beta), PDGF, and gamma-interferon (gamma-IFN). Hox 2.3 was also super-induced by serum, in the presence of cycloheximide, in cells rested previously in serum-free media, suggesting that new protein synthesis was not required for expressive augmentation. The induction of Hox 2.3, moreover, was not specific for tubular epithelium, since the gene could be activated in tubulointerstitial fibroblasts after treatment with EGF. These experiments collectively represent a first report regarding the characterization of transcripts encoding homeoboxes in adult cells derived from renal tissue. The putative DNA-binding properties of homeobox proteins in general, the prompt and rapid induction of Hox 2.3 by morphogenic cytokines in tubulointerstitial cells, and the observed effect of cycloheximide on this gene, all indicate that Hox 2.3 might have a role in the general activation of mature somatic cells, as an immediate early event, probably in the capacity of a nuclear trans-acting factor.