调节HNF4AAPEH缺陷促进UPR激活在糖尿病病中的糖尿病病
Fangfang Wang1,2, Yulin Peng1,2, Luqun Liang1,2
1Department of Pathophysiology, Basic Medical College, Guizhou Medical University, Guiyang, Guizhou Province, China.
概括
糖尿病病涉及减少的酸酶化酶 (APEH) 和肝细胞核因子4α (HNF4A),增加蛋白质碳化和细胞亡. 恢复HNF4A/APEH通路可能可以治疗DKD.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 糖尿病病 (DKD) 是末期病的主要原因,由诸如内细胞网膜应激 (ERS) 等并发症引起.
- 由活性氧物种 (ROS) 的蛋白质碳化启动的ERS激活了未折叠的蛋白质反应 (UPR) 并促进了细胞亡.
- 乙基酶酸酶 (APEH) 降解碳化蛋白质,但其在DKD中的作用尚不清楚.
研究的目的:
- 研究APEH在糖尿病病 (DKD) 中的作用和调节机制.
- 阐明APEH,肝细胞核因子4α (HNF4A),蛋白质碳化和DKD中的UPR信号之间的功能联系.
主要方法:
- 使用了24周的db/db小鼠和高葡萄糖/高脂肪刺激的管状上皮细胞.
- 采用多数据库生物信息学,形态分析和分子生物学技术.
- 进行了双露西法酶记者测定和ChIP-qPCR以确认基因调节.
主要成果:
- DKD模型显示APEH和HNF4A的表达减少,蛋白质碳化增加,并激活UPR信号.
- 证实HNF4A通过促进体结合直接调节APEH的表达.
- 在DKD中,受损的APEH功能加剧了蛋白质碳化,UPR激活和管细胞亡.
结论:
- 在DKD中,HNF4A/APEH轴在调节蛋白质碳化和UPR信号传递方面发挥着至关重要的作用.
- 减少APEH表达有助于DKD的进展,通过损害抗氧化应激和亡的保护机制.
- 准HNF4A/APEH通路为糖尿病病提供了潜在的治疗策略.
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