陈氧胆酸通过人类肝瘤 Huh7 细胞的雌激素相关受体 γ 调节纤维细胞生长因子23 基因表达
Yiwen Fan1, Hyo-Jin Kim1, Yoon Seok Jung1
1School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Republic of Korea.
Steroids
|June 10, 2023
概括
陈氧胆酸 (CDCA) 通过肝细胞中的雌激素相关受体γ (ERRγ) 增加纤维细胞生长因子23 (FGF23) 基因表达. 一种ERRγ逆agonist,GSK5182,减少了FGF23的诱导,这表明一个治疗目标.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 纤维细胞生长因子23 (FGF23) 对酸盐和维生素D的调节至关重要.
- 胆酸,如陈二氧化醇酸 (CDCA) 影响FGF19亚家族成员,但它们对FGF23的影响尚不清楚.
研究的目的:
- 研究CDCA如何影响人类肝细胞FGF23基因表达的机制.
- 确定管理高FGF23水平的潜在治疗目标.
主要方法:
- 实时PCR和西部斑分析以量化FGF23mRNA和蛋白质水平.
- 与雌激素相关的受体 γ (ERRγ) 敲击和促进活性测试.
- 使用CDCA和ERRγ逆agonist GSK5182.2.的治疗方法
主要成果:
- 在Huh7细胞中,CDCA提高了FGF23mRNA和蛋白质水平.
- CDCA还增加了ERRγ的表达,而ERRγ的淘汰消除了CDCA对FGF23.23的影响.
- 通过CDCA增强FGF23促进剂活性,部分通过ERRγ与ERRE结合进行调解.
- GSK5182 抑制了 CDCA 诱导的 FGF23 表达.
结论:
- 在人类肝细胞中,CDCA通过ERRγ升调FGF23基因表达.
- 用像GSK5182这样的抑制剂向ERRγ可能为由于胆酸失调导致FGF23升高的疾病提供治疗策略.
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