肝脏特异性的Coxsackievirus和腺病毒受体缺失会发展出与代谢功能障碍相关的脂肪肝疾病
Hong-Gi Kim1, Jin-Ho Park1, Ha-Hyun Shin1
1Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk, 367-700, Korea.
Scientific reports
|September 16, 2024
概括
与代谢功能障碍相关的脂肪肝疾病 (MAFLD) 与肥胖有关. 肝脏特异性CAR淘汰赛小鼠显示肝脏损伤和脂质积累增加,这表明CAR.
科学领域:
- 肝病学和代谢疾病
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 代谢功能障碍相关的脂肪肝疾病 (MAFLD) 是一种与肥胖和子宫外脂肪积累相关的流行肝病.
- 考克萨基病毒和腺病毒受体 (CAR) 在细胞结处起作用,与肥胖和高血压有关,但其肝功能尚不清楚.
- 肥胖小鼠肝脏中CAR水平升高,非酒精性脂肪肝炎患者的肝细胞结合处降低.
研究的目的:
- 调查Coxsackievirus和腺病毒受体 (CAR) 在肝脏中的作用,特别是在与代谢功能障碍相关的脂肪肝疾病 (MAFLD) 的背景下.
- 确定肝脏特异性CAR缺乏对饮食引起的肝损伤,脂质积累和炎症反应的影响.
- 确定潜在的CAR相互作用伙伴并阐明其调节肝脂代谢的机制.
主要方法:
- 在正常和高脂肪饮食 (HFD) 条件下,生成肝脏特异性的CAR淘汰赛 (KO) 小鼠,并与野生类型 (WT) littermates进行比较.
- 评估肝损伤,脂质积累,炎症性细胞因子转录,肝透性和巨细胞招募.
- 蛋白质拉下测定和质谱检测以确定CAR相互作用伙伴,然后对阿波利波蛋白B mRNA编辑酶催化多类3C (APOBEC3C),阿波利波蛋白B (ApoB) 和低密度脂蛋白受体 (LDLR) 表达的分析.
主要成果:
- 肝脏特异性CAR KO小鼠与WT小鼠相比,在食HFD时,肝脏损伤和脂质积累显著增加,尽管身体和肝脏重量相似.
- CAR缺乏导致炎症性细胞因子转录升高,肝脏透性增加,肝脏中巨细胞的招募增加.
- APOBEC3C被确定为一个CAR相互作用伙伴,肝脏CAR表达调节APOBEC3C水平. 卡尔科小鼠显示与APOBEC3C表达相关的ApoB和LDLR水平,这表明它在脂质调节中的作用.
结论:
- 肝脏CAR缺乏症在小鼠中加剧了饮食引起的肝损伤和脂质积累.
- 在维持肝细胞-细胞结合完整性和调节脂质代谢方面,CAR发挥着至关重要的作用,可能是通过APOBEC3C.
- 通过调节ApoB和LDLR表达,CAR缺乏会增加肝脏的透性和脂质积累,这表明CAR是MAFLD的潜在治疗标.
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