由PFOA和PFOS引起的人类肝细胞中脂质积累的新型分子途径
Xiao Gou1, Mingming Tian1, Lu Yan2
1State Environmental Protection Key Laboratory of Aquatic Ecosystem Health in the Middle and Lower Reaches of Yangtze River, School of the Environment, Nanjing University, Nanjing 210023, China.
Environment international
|August 19, 2024
概括
与PFOA和PFOS一样,和多基物质 (PFAS) 与脂肪肝疾病有关. 这项研究揭示了这些化学物质如何降低NUDT7基因的调节,增加肝脂,并可能导致NAFLD.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 和多醇基物质 (PFAS),包括 perfluorooctanoic 酸 (PFOA) 和 perfluorooctane 硫酸盐 (PFOS),是广泛存在的环境污染物.
- 暴露于PFOA和PFOS与非酒精性脂肪肝疾病 (NAFLD) 有关,但精确的分子机制尚不清楚,特别是在环境相关的度下.
研究的目的:
- 阐明PFOA和PFOS暴露导致肝细胞中脂质积累的分子机制.
- 确定关键的基因和途径参与PFAS诱导的NAFLD的人类相关剂量.
主要方法:
- 利用CRISPR-Cas9基因组查来识别受PFAS影响的NAFLD相关基因.
- 在HepG2细胞中进行了度依赖的转录试验,以评估基因表达变化.
- 综合流行病学数据挖掘,以将发现与人类暴露数据相关联.
主要成果:
- 在569个NAFLD相关基因中,NUDT7被确定为响应PFOA和PFOS暴露 (<7μM) 的显著下调基因.
- 通过PFOA和PFOS (≤10−4μM) 下调NUDT7转录导致Ace-CoA酸酶活性降低.
- 在暴露于PFOA和PFOS (<2μM) 的HepG2细胞中观察到脂肪积累增加.
结论:
- 已经确定了一种涉及PFOA和PFOS对NUDT7基因的转录下调的新机制.
- 这种机制有助于肝细胞脂质的积累,并为PFAS暴露与人类NAFLD之间的关联提供了潜在的解释.
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