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Ontogeny of renal phosphate transport and the process of growth
1Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY 10467, USA. spitzer@aecom.yu.edu
Insights
Infant kidneys reabsorb more phosphate (Pi) due to a growth-specific transporter, not NaPi-2. This explains high Pi reabsorption in growing organisms and suggests a new target for kidney research.
Area of Science:
- Nephrology
- Molecular Biology
- Pediatric Physiology
Background:
- Infant and child kidneys exhibit high phosphate (Pi) reabsorption, crucial for growth.
- This high reabsorption is linked to an elevated capacity (Vmax) of the Na+-Pi symport system.
- The molecular basis for this enhanced capacity in young organisms remains to be fully elucidated.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the high renal phosphate reabsorption in infants and children.
- To determine if a specific growth-related Na-Pi cotransporter contributes to this phenomenon.
- To differentiate the role of a potential new transporter from the known NaPi-2 transporter.
Main Methods:
- Analysis of NaPi-2 mRNA expression in young versus adult animal renal cortex.
- Oocyte expression assays using polyA RNA from animals with and without NaPi-2.
- Subtractive hybridization to isolate unique RNA sequences from young animals.
- Sequence homology analysis of isolated RNA regions with known NaPi transporters.
- Examination of Npt2 (-/-) knockout mice to assess residual Pi reabsorption.
Main Results:
- NaPi-2 mRNA levels are not elevated in young animals compared to adults.
- PolyA RNA from young animals, even after NaPi-2 depletion, induces Na+-Pi transport in oocytes.
- RNA sequences from young animals show homology to other NaPi (type II) transporters, suggesting a distinct but related transporter.
- Npt2 (-/-) knockout mice show Pi reabsorption rates higher than explained by known transporters.
Conclusions:
- The high renal phosphate reabsorption capacity in young organisms is largely attributed to a growth-specific NaPi transporter.
- This transporter is homologous to, but distinct from, previously cloned type II NaPi transporters.
- The findings suggest a novel molecular target for understanding and potentially modulating phosphate handling in pediatric kidney physiology.
Abstract:
The kidneys of infants and children reabsorb a high fraction of the filtered phosphate (Pi), as appropriate to the needs of a growing organism. This high Pi reabsorptive rate is associated with a high capacity (Vmax) of the Na+-Pi symport system. At the molecular level this high reabsorptive capacity appears to be due to the presence of a growth-specific Na-Pi cotransporter. Several experimental findings support this assumption. Firstly, the expression of NaPi-2 mRNA is, if anything, lower in the renal cortex of young animals than of adult animals. Secondly, polyA RNA obtained from growing animals depleted of NaPi-2 by specific hybridization with an antisense 16-mer induces Na+-Pi transport in oocytes. No induction of Na+-Pi transport was observed in oocytes injected with hybridized polyA RNA obtained from adult animals. Thirdly, polyA RNA derived from young rats, depleted of NaPi-2 by subtractive hybridization with adult animal renal cortical cDNA, retains its ability to encode for Na+-Pi cotransport in oocytes. Adult animal renal cortical polyA RNA, depleted of NaPi-2 by subtractive hybridization, failed to induce Na+-Pi uptake into oocytes. Fourthly, renal cortical polyA RNA from young animals, depleted of NaPi-2, contains a region that is highly homologous (80%-92%) with the corresponding region of other modulated NaPi (type II) transporters. Fifthly, this region is also present in the polyA RNA obtained from the renal cortex of newborn rats (1st week of life), despite the fact that NaPi-2 is absent at this early age. Lastly, Npt2 (-/-) knockout mice, although hypophosphatemic and phosphaturic, filter and reabsorb Pi at rates exceeding those that can be accounted for by the expression of type I and III transporters. Based on these observations it is reasonable to surmise that the high Vmax of the Na+-Pi cotransport system observed in the young is due to a large extent to the presence of a growth-specific NaPi transporter, homologous but not identical to already cloned type II NaPi transporters.