1,25-二基维生素D3调节了由氨酸介导的FGF23裂变
Han Xie1,2, Isinsu Bastepe1,2, Wen Zhou1,2
1Nephrology Division and.
JCI insight
|September 8, 2023
概括
维生素D通过维生素D受体 (VDR) 抑制furin,这种酶可以切割完整的纤维细胞生长因子23 (iFGF23). 这种机制增加了iFGF23的酸盐水平.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 矿物质的新陈代谢.
背景情况:
- 完整的纤维细胞生长因子23 (iFGF23) 被素分解成不活跃的碎片.
- 维生素D及其受体 (VDR) 参与调节furin.
- 维生素D对iFGF23裂变的影响的确切机制尚未完全理解.
研究的目的:
- 为了研究1,25-二氧维生素D3 [1,25(OH) 2D]和VDR对富林介导的IFGF23裂变的影响.
- 阐明VDR在调节的表达和活动中的作用.
- 为了确定这种途径对血清酸盐水平的影响.
主要方法:
- 使用VDR-knockout (Vdr-/-) 鼠和野生类型 (WT) 的 littermates. 使用VDR-knockout (Vdr-/-) 鼠和野生类型 (WT) 的 littermates. 使用VDR-knockout (Vdr-/-) 鼠和野生类型 (WT) 的 littermates. 使用VDR-knockout (Vdr-/-) 鼠和野生类型 (WT) 的 littermates.
- 采用了一种VDR敲除骨细胞细胞系 (OCY454).
- 评估了氨酸活性,iFGF23裂变和基因表达.
- 进行了染色体免疫沉 (ChIP) 试验.
- 分析了一项随机临床试验的数据,该试验涉及埃尔戈卡尔西费罗尔治疗.
主要成果:
- 在Vdr-/-小鼠中,iFGF23裂增加了25倍,其氨酸含量和活性增加.
- 林抑制在Vdr-/-小鼠和VDR-knockdown细胞中使iFGF23裂变正常化.
- VDR直接与富林基因上游的DNA结合,抑制其转录.
- 在WT小鼠中,林抑制增加了IFGF23和降低了血清酸盐.
- 1,25(OH) 2D治疗降低了氨酸活性,降低了iFGF23裂变,并增加了总FGF23.
- 在人类中,埃尔戈化醇治疗增加了1,25(OH) 2D,降低了furin活性和iFGF23裂变.
结论:
- 1,25(OH) 2D通过VDR介导的Furin表达的抑制来抑制IFGF23的裂变.
- 这一途径为维生素D提供了一种机制,以增加酸的IFGF23水平.
- 维生素D在调节FGF23代谢和酸盐平衡中起着至关重要的作用.
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