Suppression of parathyroid hormone production in secondary hyperparathyroidism by RNA interference

RNA干扰抑制继发性甲状旁腺功能亢进症甲状旁腺激素的产生

• 批准号: 22790807
• 负责人: KANAI Genta
• 金额: $ 2.5万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790807/
• 关键词: 人工透析学; 慢性腎不全; 二次性副甲状腺機能亢進症; RNA干渉

Secondary hyperparathyroidism(2HPT) is one of the most important complications of chronic kidney disease. Vitamin D3 receptor levels are decreased in the parathyroid glands of dialysis patients and animal models of renal failure. Recent research has shown that the functionality protein can be adjusted with the gene transfer to the parathyroid. We examined the parathyroid hormone(PTH) suppression by the RNA interference using rat 2HPT model. Serum PTH increased to a high level at the posterior when four weeks passed. Afterwards, high density anti-PTH siRNA was injected to rat's parathyroid glands. It was shown that serum PTH concentration was suppressed up to about 60%. The suppression effect was shown the peak on 1-2 weeks, and, then, maintained limitedly. In the present study, it was suggested that using the atelocollagen that was non-viruses drug delivery system contribute to the extension of effectiveness.

继发性甲状旁腺功能亢进（2HPT）是慢性肾脏疾病最重要的并发症之一。透析患者和肾功能衰竭动物模型甲状旁腺中维生素D3受体水平降低。最近的研究表明，功能蛋白可以随着基因转移到甲状旁腺而调整。采用大鼠2HPT模型，研究RNA干扰对甲状旁腺激素（PTH）的抑制作用。四周后血清甲状旁腺素升高至较高水平。随后，将高密度抗甲状旁腺siRNA注射到大鼠甲状旁腺。结果表明，血清甲状旁腺激素浓度被抑制约60%。抑制效果在1 ~ 2周达到峰值，然后有限度地维持。在本研究中，我们认为使用非病毒的胶原细胞给药系统有助于延长药物的有效性。

项目成果

RNA干渉による二次性副甲状腺機能亢進症治療法の開発

RNA干扰治疗继发性甲状旁腺功能亢进症的进展

• 发表时间: 2011
• 作者: 金井厳太;角田隆俊;澤田佳一郎;深川雅史
• 通讯作者: 深川雅史

Gene therapy for secondary hyperparathyroidism

继发性甲状旁腺功能亢进症的基因治疗

• 发表时间: 2010
• 期刊: Clinical Calcium
• 作者: Kanai G;Fukagawa M
• 通讯作者: Fukagawa M