Upregulation of rat intestinal uroguanylin mRNA by dietary zinc restriction

A cDNA for the rat uroguanylin precursor was identified, by differential display of intestinal mRNA, as upregulated in zinc-deficient rats and subsequently was cloned. The cDNA and deduced amino acid sequences show a high degree of homology to human and opossum preprouroguanylin sequences. When used as a probe for Northern blot analysis of RNA from rat intestinal mucosa, the uroguanylin cDNA hybridized to a single species of mRNA that was 2.5-fold more abundant in zinc deficiency. A tissue distribution survey indicates that although the small intestine expresses a disproportionately high level of preprouroguanylin, this hormone precursor is also expressed in the colon, stomach, kidney, thymus, and testis. The induction by zinc deficiency is the first reported case of gene regulation for this hormone. These results also suggest a potential mechanism to explain, at least in part, the beneficial effects of zinc supplementation for secretory diarrhea prevalent in many areas of the world.