在LSEC中MVB的自性降解促进了阿尔多素诱导的HSC激活
Tingting Chen1,2, Yan Zhang1,2, Yijie Zhang1,2
1Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, No. 1838, North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, China.
Hepatology international
|June 18, 2023
概括
阿尔多 (Aldo) 通过自性损害肝脏侧侧内皮细胞 (LSEC) 外细胞囊泡 (EV) 产生,恶化肝脏纤维化. 针对LSEC自和EV分泌提供了一种潜在的肝纤维化治疗方法.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞外囊泡 (EVs) 在肝纤维化中起着关键作用.
- 来自肝脏侧侧内皮细胞 (LSEC) 的EVs在肝星细胞 (HSC) 激活和肝纤维化中的特定作用尚不清楚.
- 阿尔多 (Aldo) 可能通过自性调节LSEC衍生的EVs.
研究的目的:
- 调查Aldo在监管来自LSECs的电动汽车中的作用.
- 阐明Aldo影响LSEC-EVs的机制及其对肝纤维化的贡献.
主要方法:
- 阿尔多连续抽的老鼠模型.
- 在体外LSEC培养与阿尔多刺激.
- 传输电子显微镜 (TEM) 用于超结构分析.
- 使用si-ATG5腺相关病毒 (AAV) 进行自抑制.
- 用于EV特征的RNA测序和纳米粒子跟踪 (NTA).
- 使用si-RAB27a AAV.抑制EV分泌
主要成果:
- 阿尔多诱导了大鼠的肝纤维化和LSEC毛细化.
- 阿尔多通过增加ATP6V0A2.2,在LSEC中提高了自和降解的多胞体 (MVBs).
- 在LSEC中抑制自减轻了阿尔多诱导的肝纤维化.
- 阿尔多降低了LSEC衍生的EV的数量和质量,包括减少的miRNA-342-5P.
- 抑制EV分泌促进了肝纤维化和HSC激活.
结论:
- 在LSEC中MVB的Aldo诱导的自降解减少了EV的数量和质量.
- 这种EVs的减少有助于高血小板激活和肝纤维化在hyperaldosteronism.
- 调节LSEC自和EV分泌是一种潜在的肝纤维化治疗策略.
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