Regulation of the human sodium-phosphate cotransporter NaPi-IIb gene promoter by epidermal growth factor

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Abstract
The intestinal sodium-phosphate cotransporter (NaPi-IIb) plays a major role in intestinal Piabsorption. Epidermal growth factor (EGF) is involved in the regulation of Pihomeostasis. However, the role of EGF in intestinal NaPi-IIb regulation is not clear. The current studies showed that EGF decreased NaPi-IIb mRNA abundance by 40–50% in both rat intestine and Caco-2 cells. To understand the mechanism of this regulation, we cloned the human NaPi-IIb gene and promoter region and studied the effect of EGF on NaPi-IIb gene transcription. The human NaPi-IIb gene has 12 exons and 11 introns. Two transcription initiation sites were identified by primer extension. Additionally, 2.8 kb of the 5′-flanking region of the gene was characterized as a functional promoter in human intestinal (Caco-2) and human lung (A549) cells. Additional studies showed that EGF inhibited promoter activity by 40–50% in Caco-2 cells and that actinomycin D treatment abolished this inhibition. EGF had no effect on promoter activity in lung (A549) cells. We conclude that the human NaPi-IIb gene promoter is functional in Caco-2 and A549 cells and that the gene is responsive to EGF by a transcriptionally mediated mechanism in intestinal cells.

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