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ZHX3 与 CEBPB 相互作用,抑制肝脏葡萄糖原基因表达和尿酸分泌

Wei Xuan Tan^1,2, Lillian Yuxian Lim¹, Nesha Afsha¹

¹Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.

|February 24, 2025

概括

ZHX3蛋白抑制肝细胞中的葡萄糖基因,影响尿酸水平和2型糖尿病风险. 它在胰腺β细胞中的作用不受ZHX3删除的影响.

科学领域:

代谢调节代谢调节代谢调节
分子内分泌学分子内分泌学
转录控制转录控制

背景情况:

尚不完全了解ZHX3在葡萄糖代谢和2型糖尿病 (T2D) 风险中的作用.
ZHX3是一种转录抑制剂,与禁食血糖 (FBG) 水平和T2D风险有关.

研究的目的:

研究ZHX3在葡萄糖代谢中的功能.
阐明ZHX3影响FBG水平和T2D风险的分子机制.

主要方法:

在人类胰腺β细胞系 (EndoC-βH1) 和人类肝瘤细胞系 (HepG2) 中进行基因删除研究.
转录组分析以确定基因表达变化.
测量胰岛素分泌和尿酸水平.
同免疫沉和质谱测量以确定蛋白质相互作用.

主要成果:

在EndoC-βH1细胞中ZHX3的删除没有影响葡萄糖刺激胰岛素分泌 (GSIS) 或转录组.
在HepG2细胞中,ZHX3抑制葡萄糖原基因 (PCK1,G6PC1).
缺少ZHX3会在HepG2细胞中调节尿酸载体基因 (SLC17A1),导致尿酸分泌量增加.
尿酸升高会损害EndoC-βH1细胞中的GSIS.
CEBPB被确定为ZHX3结合伙伴,参与抑制PCK1,G6PC1和SLC17A1转录.

结论:

ZHX3在肝细胞中调节葡萄糖代谢方面发挥着关键作用.
ZHX3通过其调节葡萄糖生成基因和尿酸运输,影响FBG水平和T2D风险.
对于这个监管功能来说,ZHX3和CEPB的相互作用是必不可少的.

关键词:

在SLC17A1中.在 ZHX3 的位置上.肝脏中的葡萄糖生产.2 型糖尿病 2 型糖尿病尿酸是什么尿酸是什么

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