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Published on: December 9, 2022
Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice
Hiroko Segawa1, Setsuko Yamanaka, Yasue Ohno
1Dept. of Molecular Nutrition, Institution of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
American Journal of Physiology. Renal Physiology
|September 21, 2006
Summary
Klotho deficiency causes hyperphosphatemia in mice due to impaired renal sodium-phosphate cotransporter expression and trafficking, not altered intestinal phosphate absorption. This highlights klotho
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Klotho protein is crucial for calcium and phosphate balance.
- Dysregulation of klotho impacts mineral homeostasis.
Purpose of the Study:
- Investigate sodium-phosphate (Na-Pi) cotransporter regulation in klotho-deficient (kl/kl) mice.
- Determine the role of klotho in phosphate handling and related transporter expression.
Main Methods:
- Comparative analysis of kl/kl mice and wild-type littermates.
- Assessment of plasma biochemistry, renal and intestinal transporter activity, protein, and mRNA levels.
- Dietary manipulation (low phosphate) and pharmacological treatment (colchicine) to study transporter expression and trafficking.
Main Results:
- Kl/kl mice exhibited hyperphosphatemia, elevated 1,25(OH)2D3, and increased renal/intestinal Na-Pi cotransporter activity and protein levels (types IIa, IIb, IIc).
- Renal type IIa/IIc transporter mRNA levels were decreased, while type IIb mRNA was unchanged in kl/kl mice.
- Plasma FGF23 levels were significantly higher in kl/kl mice; low phosphate diet normalized klotho and decreased FGF23.
- Abnormal membrane trafficking of type IIa transporter and impaired apical membrane insertion were observed in kl/kl mice.
Conclusions:
- Hyperphosphatemia in klotho-deficient mice stems from dysregulated expression and apical membrane trafficking of renal type IIa/IIc sodium-phosphate cotransporters.
- Intestinal phosphate uptake does not appear to be the primary driver of hyperphosphatemia in this model.
- Klotho plays a critical role in regulating renal phosphate excretion through modulation of Na-Pi cotransporter function and localization.
