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Abstract: TH-PO536

Cell Cycle Acceleration in Parathyroid Glands Is Caused by the Combination of CKD Environment and High-Phosphorus Diet in the Adenine Rat Model Because of Suppression of CDKN1B Expression

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Uchiyama, Taketo, Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
  • Ohkido, Ichiro, Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
  • Nakashima, Akio, The Jikei University School of Medicine, Tokyo, Japan
  • Saito, Yatsumu, The Jikei University School of Medicine,Tokyo,Japan, Tokyo, Japan
  • Yokoo, Takashi, The Jikei University School of Medicine, Tokyo, Japan
Background

Chronic kidney disease (CKD) disrupts mineral homeostasis and is characterized by secondary hyperparathyroidism (SHPT). SHPT is characterized by abnormally increased proliferation of parathyroid cells, although the underlying mechanism remains largely unknown. Previously, we reported that an increase in Ki67 immunohistochemical expression was observed in 5/6 nephrectomy rats fed the high phosphorus diet. The aim of this study was to investigate the role of the CKD environment with and without high-phosphorus diet in SHPT progression, particularly cell cycle acceleration in the parathyroid glands.

Methods

CKD was induced by a diet containing 0.75% adenine. For 2 weeks, few CKD rats and few control rats were fed diets containing 0.9% phosphorus (normal phosphate diet); other CKD rats and control rats were fed diets containing 1.3% phosphorus (high-phosphate diet). In a gene expression analysis related with cell cycle, such as CDKs, CKIs and cyclins, TaqMan probes were used to conduct quantitative polymerase chain reactions. Ki67 and cyclin-Dependent kinase inhibitor 1B (CDKN1B) protein expressions were analyzed immunohistochemically.

Results

Among the CKD rats, there was no significant difference in severity of CKD status between those fed the normal phosphorus diets (CKD NP rats) and those fed the high-phosphorus diets (CKD HP rats); however, the increase in Ki67 immunohistochemical expression in cells was observed in only CKD HP rats (Figure 1). Thus, SHPT and severe CKD-mineral and bone disorder status were induced only by high-phosphorus diets in CKD rats. CDKN1B expression, which plays an important role in the G1/S checkpoint, was significantly decreased only in CKD HP rats (Figure 2).

Conclusion

Only CKD HP rats showed a significant reduction in CDKN1B gene and protein expression. Our data indicated that CDKN1B plays a major role SHPT progression and cell cycle acceleration and is an important target in SHPT therapy.