Phosphate transport by fibroblasts from patients with hypophosphataemic vitamin D-resistant rickets.
It is accepted that renal phosphate wasting is the basis of hypophosphataemia in vitamin D-resistant hypophosphataemic rickets (VDRR). Abnormal renal adaptation to phosphate deprivation has also been reported in these patients. We studied sodium-dependent phosphate transport and its modulation by phosphate deprivation in skin fibroblasts cultured from healthy subjects and patients with VDRR. Control fibroblasts exhibited high-affinity sodium-dependent phosphate transport (77 +/- 12 mumol/l) which resembled the ubiquitous transport of renal and non-renal cells. Phosphate deprivation (incubation in low phosphate medium) increased the maximal velocity (Vmax) of the transport by 2.7-fold after 24 h, with no change in the affinity. The increase in Vmax was dependent on gene transcription and protein synthesis. The sodium-dependent phosphate transport exhibited in fibroblasts from VDRR patients did not significantly differ from that of control subjects, except that the Vmax of the phosphate transport was higher in cells from patients with VDRR under normal and phosphate-deprivation conditions, although the difference was significant only after 24 h of phosphate deprivation (Vmax: 22.6 +/- 2.4 pmol/mg protein per s in VDRR vs 16 +/- 3.6 pmol/mg protein per s in controls, P less than 0.05). These data demonstrate that sodium-coupled phosphate transport in human skin fibroblasts has the properties of ubiquitous sodium-phosphate co-transport and show that this transport is not deficient in patients with VDRR. Indeed paradoxically the Vmax was 40% higher in VDRR than in control subjects after 24 h of phosphate deprivation. The transport must be either different from that of kidney cells responsible for the phosphate leak, or differently modulated.(ABSTRACT TRUNCATED AT 250 WORDS)
Escoubet
B
B
INSERM U251, Faculté de Médecine X Bichat, Université Paris 7, France.
Silve
C
C
Balsan
S
S
Amiel
C
C
D000293:Adolescent; D000328:Adult; D001692:Biological Transport / Q000502:physiology; D002117:Calcitriol / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000502:physiology; D010446:Peptide Fragments / Q000502:physiology; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D012964:Sodium / Q000502:physiology; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; D019379:Teriparatide; D012964:Sodium; D002117:Calcitriol