在人类MASH中,SARS-CoV-2受体ACE2通过脂肪酸进行上调
Luis Cano1, Lise Desquilles1, Gevorg Ghukasyan2
1INSERM, INRAE, Univ Rennes 1, Nutrition Metabolisms and Cancer, Rennes, France.
JHEP reports : innovation in hepatology
|December 11, 2023
概括
与代谢功能障碍相关的脂肪性肝病 (MASLD) 增加了血管素转化酶2 (ACE2) 的可用性,这是SARS-CoV-2的关键受体. 在MASLD中的脂质过载和炎症有助于更高的ACE2表达,增加COVID-19严重性风险.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 与代谢功能障碍相关的脂肪性肝病 (MASLD) 与COVID-19中肝损伤增加有关.
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 使用血管素转化酶2 (ACE2) 作为其主要受体.
- 了解肝病中的ACE2表达对于评估COVID-19脆弱性至关重要.
研究的目的:
- 研究MASLD和其他纤维炎性肝病中ACE2的表达水平和细胞来源.
- 为了确定年龄,肝脏脂肪和炎症等因素如何影响ACE2可用性.
- 探索炎症性细胞因子和脂肪酸对ACE2 mRNA表达的体外影响.
主要方法:
- 对MASLD和纤维炎性肝病数据集的转录基因分析.
- 肝脏微环境中的免疫细胞群体的解体.
- 多重复合免疫组织化学,单细胞RNA测序和批量转录组学以识别表达ACE2的细胞.
- 在人体初级肝细胞上的体外实验.
主要成果:
- ACE2在肝细胞,肝脏侧侧内皮细胞,胆管管,胆管细胞和毛细血管中表达.
- 在MASLD中,ACE2的表达随着年龄的增长,肝脏脂肪,炎症和纤维化增加.
- 长链脂肪酸在肝细胞中对ACE2mRNA进行上调,而炎症性细胞因子则对其进行下调.
结论:
- 脂肪肝疾病中的脂质过载会提高ACE2受体的可用性.
- 在MASLD中ACE2的增加可能解释了对严重COVID-19和肝损伤的高度易感性.
- 针对影响ACE2表达的因素,可以为脆弱患者提供保护策略.
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