肝胆健康与疾病中的细胞外小泡。

IF 4.2 2区 医学 Q1 PHYSIOLOGY
Gopanandan Parthasarathy, Petra Hirsova, Enis Kostallari, Guneet S Sidhu, Samar H Ibrahim, Harmeet Malhi
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引用次数: 0

摘要

细胞外小泡是细胞释放的膜结合纳米颗粒,是生理和病理状态下细胞间通讯的重要手段。我们概述了EV生物发生、货物选择、受体细胞效应以及分离和表征技术中的关键考虑因素的最新进展。由于体内研究内源性纳米颗粒的技术限制,对EVs生理作用的研究依赖于基于细胞的模型系统。最近的几项研究阐明了EVs在肝病中的机制作用,包括非酒精性脂肪肝、病毒性肝炎、胆汁淤积性肝病、酒精相关性肝病、急性肝损伤和肝癌。利用疾病模型和人类样本,详细讨论了脂毒性EVs通过细胞内激活应激信号在内质网应激和微泡下游的生物发生。EVs的各种货物,包括蛋白质、脂质和核酸,可以以疾病特异性的方式富集。通过携带不同的货物,EVs可以直接赋予致病潜力,例如,NASH中单核细胞衍生的巨噬细胞的募集和激活,以及肝细胞癌的致瘤性和化疗耐药性。我们讨论了EVs货物的致病作用以及EVs在受体细胞中激活的信号通路。我们回顾了EVs可以作为肝胆疾病的生物标志物的文献。此外,我们描述了设计电动汽车向特定细胞类型传递调节信号的新方法,从而将其用作肝病的治疗穿梭机。最后,我们确定了这一有前景的发现和发展领域的关键缺陷和未来方向。©2023美国生理学会。Compr Physiol 13:4631-46582023。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Extracellular Vesicles in Hepatobiliary Health and Disease.

Extracellular vesicles (EVs) are membrane-bound nanoparticles released by cells and are an important means of intercellular communication in physiological and pathological states. We provide an overview of recent advances in the understanding of EV biogenesis, cargo selection, recipient cell effects, and key considerations in isolation and characterization techniques. Studies on the physiological role of EVs have relied on cell-based model systems due to technical limitations of studying endogenous nanoparticles in vivo . Several recent studies have elucidated the mechanistic role of EVs in liver diseases, including nonalcoholic fatty liver disease, viral hepatitis, cholestatic liver disease, alcohol-associated liver disease, acute liver injury, and liver cancers. Employing disease models and human samples, the biogenesis of lipotoxic EVs downstream of endoplasmic reticulum stress and microvesicles via intracellular activation stress signaling are discussed in detail. The diverse cargoes of EVs including proteins, lipids, and nucleic acids can be enriched in a disease-specific manner. By carrying diverse cargo, EVs can directly confer pathogenic potential, for example, recruitment and activation of monocyte-derived macrophages in NASH and tumorigenicity and chemoresistance in hepatocellular carcinoma. We discuss the pathogenic role of EVs cargoes and the signaling pathways activated by EVs in recipient cells. We review the literature that EVs can serve as biomarkers in hepatobiliary diseases. Further, we describe novel approaches to engineer EVs to deliver regulatory signals to specific cell types, and thus use them as therapeutic shuttles in liver diseases. Lastly, we identify key lacunae and future directions in this promising field of discovery and development. © 2023 American Physiological Society. Compr Physiol 13:4631-4658, 2023.

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来源期刊
CiteScore
10.50
自引率
0.00%
发文量
38
审稿时长
6-12 weeks
期刊介绍: Comprehensive Physiology is the most authoritative and comprehensive collection of physiology information ever assembled, and uses the most powerful features of review journals and electronic reference works to cover the latest key developments in the field, through the most authoritative articles on the subjects covered. This makes Comprehensive Physiology a valued reference work on the evolving science of physiology for both researchers and clinicians. It also provides a useful teaching tool for instructors and an informative resource for medical students and other students in the life and health sciences.
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