Abstract: TH-PO1061
Phosphate Retention Induces Growth Retardation in Adolescent Mice
Session Information
- Mineral Disease: Ca/Mg/PO4
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Mineral Disease
- 1201 Mineral Disease: Ca/Mg/PO4
Authors
- Kohara, Marina, Jichi Medical University, Shitsuke, Japan
- Shiizaki, Kazuhiro, Jichi Medical University, Shitsuke, Japan
- Iwazu, Yoshitaka, Jichi Medical University, Shitsuke, Japan
- Miura, Yutaka, Jichi Medical University, Shitsuke, Japan
- Akiyama, Kenichi, Tokyo Women's Medical University, Tokyo, Japan
- Nakano, Toshihiro, Tokyo Women's Medical University, Tokyo, Japan
- Kaneda, Ruri, Jichi Medical University, Shitsuke, Japan
- Kurosu, Hiroshi, Jichi Medical University, Shitsuke, Japan
- Kuro-o, Makoto, Jichi Medical University, Shitsuke, Japan
Background
Growth retardation is a major problem of chronic kidney disease (CKD) in adolescence. It is well known that the effect of supplementation of growth hormone (GH) is not sufficient, so more effective treatments have been requiring. CKD causes the phosphate retention and this control is very difficult due to the nutritional concern. We hypothesized that phosphate retention might be one of pathogenesis of growth retardation in adolescence with CKD.
Methods
Female C57BL/J6 mice were fed the regulated diets consists of various amount of phosphate from four to eight weeks old. Body weight, femur length and serum phosphate and insulin-like growth factor-1 (IGF-1) levels were measured. The target genes of GH including IGF-1, acid-labile subunit (ALS), major urinary proteins (MUP) 1 and 3, solute carrier organic anion transporter family member 1a1 (SLCO1A1), and hydroxysteroid dehydrogenase 3β5 (HSD3B5) mRNA, IGF-1 binding protein-1 (IGFBP-1) mRNA as an inhibitory marker of IGF-1 signaling and signal transducers and activators of transcription (STAT) 5 protein levels were evaluated in liver.
Results
The remarkable growth retardation with significantly high phosphate and low IGF-1 levels in serum were confirmed in mice fed the highest phosphate diet. The significantly lower expression levels in all of target genes of GH and STAT5 protein, and higher expression level in IGFBP-1 mRNA were also observed. The mice fed the middle phosphate diets showed the significantly lower levels in serum IGF-1 and in target gene expressions of GH compared with those fed the normal phosphate diet but not growth retardation.
Conclusion
The phosphate retention induces the growth retardation resulting from the inhibitions of both GH and IGF-1 signaling. Its moderate restriction might improve the growth retardation resulting from the improvement of the resistance to IGF-1 even though serum IGF-1 level was low. These findings suggest that the controlling phosphate retention using the phosphate binders and dietary restriction should be considered in adolescent CKD patients who require the supplementation of GH.