改变拼接因子和替代拼接事件在饮食和多双诱导的肝病的小鼠模型中
Belinda J Petri1, Kellianne M Piell1, Banrida Wahlang2
1Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Environmental toxicology and pharmacology
|September 8, 2023
概括
聚二 (PCB) 和高脂肪饮食破坏肝脏的拼接因素和替代拼接事件,可能导致非酒精性脂肪肝疾病 (NAFLD) 进展为NASH.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
- 环境健康 环境健康
背景情况:
- 非酒精性脂肪肝疾病 (NAFLD) 与环境中多二 (PCB) 暴露有关.
- 在肥胖性肝病中观察到替代拼接 (AS) 失调,受拼接因子 (SFs) 和m6A修改的影响.
研究的目的:
- 调查高脂肪饮食 (HFD) 和PCB暴露对肝脏SF和AS事件的影响.
- 确定有助于NAFLD病变的特定分子机制.
主要方法:
- 来自暴露于HFD和PCB的小鼠肝脏mRNA测序数据的综合分析 (Aroclor1260,PCB126).
- 利用转录拼接的复制多变量分析 (rMATS) 来识别差异性AS事件 (ASEs).
主要成果:
- 同时暴露于Aroclor1260和PCB126改变了100个SFs.
- 在366个与NAFLD途径相关的基因中确定了449个ASE,类似于m6A修饰扰动.
- 通过HFD和PCB暴露,证明了肝脏SF和AS调节机制的破坏.
结论:
- 暴露于HFD和PCB会破坏肝脏SF和AS,导致异构体表达的改变.
- 这些变化可能会导致NAFLD进展为非酒精性脂肪肝炎 (NASH).
- 突出了与NAFLD中SF和AS相关的潜在治疗目标.
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