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Abstract: PO0314

Cell Cycle Acceleration in Parathyroid Glands Is Caused by the Suppression of LncRNA Gas5 Expression in the Presence of a High-Phosphorus Diet in an Adenine-Induced CKD Rat Model

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic


  • Uchiyama, Taketo, Jikei University School of Medicine, Minato-ku, Tokyo, Japan
  • Ohkido, Ichiro, Jikei University School of Medicine, Minato-ku, Tokyo, Japan
  • Saito, Yatsumu, Jikei University School of Medicine, Minato-ku, Tokyo, Japan
  • Nakashima, Akio, Jikei University School of Medicine, Minato-ku, Tokyo, Japan
  • Yokoo, Takashi, Jikei University School of Medicine, Minato-ku, Tokyo, Japan

Chronic kidney disease (CKD), especially secondary hyperparathyroidisim (SHPT), is strongly associated with systemic calcification, including that in blood vessels. Therefore, it is important to elucidate its underlying pathological mechanism. SHPT is characterized by an unusually increased proliferation of parathyroid cells. We analyzed the expression of multiple cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors and demonstrated that the accelerated cell cycle in SHPT is caused by a reduction in CDKN1B expression (ASN 2019). To investigate the mechanism underlying SHPT development, we analyzed factors regulating CDKN1B expression in the parathyroid gland using two phosphorus-containing diets in a rat model of adenine-induced CKD.


CKD was induced by a diet containing 0.75% adenine. For 5 days, few rats in the CKD and control groups were fed a diet containing 0.9% phosphorus, and the remaining were fed a diet containing 1.3% phosphorus. We investigated the expression levels of approximately 20 miRNAs, such as miR-221, known to regulate CDKN1B expression, as well as the long noncoding RNA Gas5, using TaqMan probes for quantitative polymerase chain reactions.


There were no significant differences in miRNA expression levels among the four groups (Figure 1). Gas5, known to be downregulated in prostate cancer cell, directly upregulates CDKN1B expression and further interacts with E2F1, which binds and activates CDKN1B. This strengthens the binding between E2F1 and CDKN1B stronger. It was observed that the expression of Gas5 was significantly decreased when the high-phosphorus diet was added to the CKD environment, and E2F1 expression did not change significantly (Figure 2).


These results suggest that parathyroid cell proliferation might be due to the suppression of Gas5 expression in response to the addition of the high-phosphorus diet to the CKD environment, with a subsequent reduction in CDKN1B expression.