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

• Published in: American Journal of Physiology: Cell Physiology 2001-03, Vol.280 (3), p.C628-C636
• Main Authors: Xu, Hua, Collins, James F., Bai, Liqun, Kiela, Pawel R., Ghishan, Fayez K.
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.280.3.C628

The intestinal sodium-phosphate cotransporter (NaP i -IIb) plays a major role in intestinal P i absorption. Epidermal growth factor (EGF) is involved in the regulation of P i homeostasis. However, the role of EGF in intestinal NaP i -IIb regulation is not clear. The current studies showed that EGF decreased NaP i -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 NaP i -IIb gene and promoter region and studied the effect of EGF on NaP i -IIb gene transcription. The human NaP i -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 NaP i -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.