Chronic kidney disease (CKD) disrupts mineral homeostasis and its main underlying cause is secondary hyperparathyroidism (SHPT). We previously reported that calcium-sensing receptor (CaSR) mRNA and protein expression in parathyroid glands (PTGs) significantly decreased in a CKD rat model induced by a 5/6 nephrectomy that were fed a high phosphorus diet. However, there was a significant difference in the severity of CKD between high phosphorus and adequate phosphorus diet groups. Thus, it was unclear whether CKD environment or the high phosphorus diet influenced CaSR expression, and the underlying mechanism remains largely unknown. CKD was induced in rats with 0.75% adenine-containing diet. CKD and control rats were maintained for 5 days and 2 weeks on diets with 0.7% or 1.3% phosphorus. For gene expression analysis, quantitative real-time polymerase chain reaction was performed with TaqMan probes. Protein expression was analyzed by immunohistochemistry. PTG CaSR expression significantly decreased in the presence of a severe CKD environment, even without the high phosphate load. Ki67 expressing cells in PTGs were significantly higher only in the CKD rats fed a high phosphorus diet. Furthermore, among the many genes that could affect CaSR expression, only vitamin D receptor (VDR) and glial cells missing 2 (Gcm2) showed significant changes. Moreover, Gcm2 was significantly reduced at an early stage without significant changes in serum calcium, phosphorus and 1,25(OH)2 vitamin D, and there was no significant reduction in CaSR and VDR expressions. Then, significantly elevated Ki67-positive cell numbers were also only observed in the early CKD PTGs with high-phosphorus diets. Our data suggest that the cause of the decreased PTG CaSR expression is the reduction in VDR and Gcm2 expression; Gcm2 may play a role in the onset and progression of SHPT.

中文翻译：

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即使没有高磷饮食，严重的慢性肾病环境也会降低腺嘌呤诱导大鼠甲状旁腺中钙敏感受体的表达。

慢性肾病 (CKD) 会破坏矿物质稳态，其主要原因是继发性甲状旁腺功能亢进 (SHPT)。我们之前报道过，在以高磷饮食喂养的 5/6 肾切除术诱导的 CKD 大鼠模型中，甲状旁腺 (PTG) 中的钙敏感受体 (CaSR) mRNA 和蛋白质表达显着降低。然而，高磷和足磷饮食组之间 CKD 的严重程度存在显着差异。因此，目前尚不清楚 CKD 环境或高磷饮食是否影响 CaSR 表达，其潜在机制仍很大程度上未知。CKD 在大鼠中被诱导为含 0.75% 腺嘌呤的饮食。CKD 和对照大鼠在含 0.7% 或 1.3% 磷的饮食中维持 5 天和 2 周。对于基因表达分析，使用 TaqMan 探针进行实时定量聚合酶链反应。通过免疫组织化学分析蛋白质表达。PTG CaSR 表达在严重 CKD 环境中显着降低，即使没有高磷酸盐负荷。仅在喂食高磷饮食的 CKD 大鼠中，PTG 中的 Ki67 表达细胞显着更高。此外，在影响 CaSR 表达的众多基因中，只有维生素 D 受体（VDR）和缺失 2 的神经胶质细胞（Gcm2）表现出显着变化。此外，Gcm2 早期显着降低，血清钙、磷和 1,25(OH)2 维生素 D 没有显着变化，CaSR 和 VDR 表达没有显着降低。然后，仅在具有高磷饮食的早期 CKD PTG 中也观察到显着升高的 Ki67 阳性细胞数量。我们的数据表明 PTG CaSR 表达降低的原因是 VDR 和 Gcm2 表达的降低；Gcm2 可能在 SHPT 的发生和进展中发挥作用。