维生素D可以切换BAF复合体以保护β细胞
Zong Wei1, Eiji Yoshihara1, Nanhai He1
1Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cell
|May 15, 2018
概括
维生素D受体 (VDR) 在保护胰腺β细胞免受2型糖尿病 (T2D) 炎症和功能障碍方面发挥着至关重要的作用. 针对VDR-染色体相互作用为T2D提供了新的治疗策略.
科学领域:
- 内分泌学
- 分子生物学
- 免疫学
背景情况:
- 2型糖尿病 (T2D) 具有由炎症和胰岛素抵抗驱动的β细胞功能障碍的特征.
- 预防β细胞枯竭仍然是控制T2D进展的重要治疗障碍.
研究的目的:
- 研究维生素D受体 (VDR) 在调节炎症和β细胞存活中的作用.
- 识别与VDR相关的蛋白质复合物及其在T2D环境中的功能.
主要方法:
- 研究了与主蛋白 (BRD7,BRD9) 和染色体重塑复合物 (PBAF,BAF) 的VDR相互作用.
- 分析了VDR对染色体可访问性和增强剂活性的全基因组影响.
- 在T2D小鼠模型中利用了BRD9的药理抑制.
主要成果:
- 它可以调节炎症和β细胞存活率.
- 通过乙化和原蛋白介导的VDR与PBAF染色体重塑复合物相关.
- 结合体的VDR促进PBAF的结合,从而产生抗炎作用.
- 抑制BRD9增强PBAF-VDR关联,恢复β细胞功能,改善糖尿病小鼠的高血糖.
结论:
- 鉴定了一种非特征化的依赖于VDR的转录途径,对T2D中的β细胞存活至关重要.
- VDR:PBAF/BAF关联代表了T2D治疗的潜在治疗目标.
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