Identification of a new gene product (diphor-1) regulated by dietary phosphate

Chronic restriction of dietary P-i elicits an increased reabsorption of P-i in the kidney proximal tubules, which involves a stimulation of apical Na-P-i cotansport. This adaptation is in part a direct cellular response of which the mechanism(s) are poorly understood. In this study, the impact of dietary P-i restriction on the differential expression of rat kidney cortex mRNAs was visualized to identify gene products regulated by the P-i status. When kidney cortex mRNAs of rats fed a low-or a high-P-i diet were compared by differential display-polymerase chain reaction (DD-PCR), thirty modulated cDNA bands were observed, of which four were confirmed as being regulated. We focused on one of the upregulated bands, dietary P-i-regulated RNA-1 (diphor-1). A cDNA containing an open reading frame encoding a 52-kDa protein was cloned by library screening. Diphor-1 exhibits a high degree of identity to the Na/H exchanger regulatory factor and to a tyrosine kinase activating protein. Highest expression of diphor-1 mRNA was detected in the kidney (proximal tubules) and in small intestine. Expression experiments showed that diphor-1 specifically increases Na-P-i cotransport in oocytes of Xenopus laevis coinjected with renal type II Na-P-i cotransporter cRNA. Further characterizations of diphor-1 will show whether diphor-1 is primarily or secondarily involved in the response to dietary P-i.