Dietary regulation of renal phosphate transporters in hypophosphatemic mice

Abstract:

X-linked hypophosphatemic rickets (XLH) is known to impair renal adaptive response to Pi restriction. We investigated the effects of dietary Pi on the synthesis of renal sodium-dependent inorganic phosphate (Na/Pi) cotransporters (Npt1 and NaPi-7) in X-linked hypophosphatemic mice (Hyp). The NaPi-7 mRNA level in Hyp mice was reduced to 50% of that of normal mice while the Npt1 mRNA level was unchanged. After feeding a low-Pi diet, the amounts of NaPi-7 protein and mRNA were markedly increased in both normal and Hyp mice. In contrast, after feeding a high-Pi diet, the levels of protein and mRNA were largely decreased in both mice. Immunohistochemical analysis indicated that NaPi-7 staining was largely enhanced in the apical membrane of renal proximal tubular cells in the normal and Hyp mice fed the low-Pi diet. In contrast, NaPi-7 staining was decreased in both groups of rats fed the high-Pi diet. Npt1 immunoreactivity was detected in the apical membrane of proximal convoluted and straight tubular cells in Hyp and normal mice, and was unchanged regardless of dietary Pi manipulation in both mice. Thus, dietary regulation for the synthesis of the two cotransporters is not impaired in Hyp mice.