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自噬与肝脏疾病中的 microRNA 失调

Autophagy and microRNA dysregulation in liver diseases.

机构信息

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Sillim-dong, Kwanak-gu, Seoul, 151-742, Korea.

出版信息

Arch Pharm Res. 2014;37(9):1097-116. doi: 10.1007/s12272-014-0439-9. Epub 2014 Jul 12.

Abstract

Autophagy is a catabolic process through which organelles and cellular components are sequestered into autophagosomes and degraded via fusion with lysosomes. Autophagy plays a role in many physiological processes, including stress responses, energy homeostasis, elimination of cellular organelles, and tissue remodeling. In addition, autophagy capacity changes in various disease states. A series of studies have shown that autophagy is strictly controlled to maintain homeostatic balance of energy metabolism and cellular organelle and protein turnover. These studies have also shown that this process is post-transcriptionally controlled by small noncoding microRNAs that regulate gene expression through complementary base pairing with mRNAs. Conversely, autophagy regulates the expression of microRNAs. Therefore, dysregulation of the link between autophagy and microRNA expression exacerbates the pathogenesis of various diseases. In this review, we summarize the roles of autophagy and microRNA dysregulation in the course of liver diseases, with the aim of understanding how microRNAs modify key autophagic effector molecules, and we discuss how this dysregulation affects both physiological and pathological conditions. This article may advance our understanding of the cellular and molecular bases of liver disease progression and promote the development of strategies for pharmacological intervention.

摘要

自噬是一种分解代谢过程,通过该过程,细胞器和细胞成分被隔离到自噬体中,并通过与溶酶体融合而降解。自噬在许多生理过程中发挥作用,包括应激反应、能量稳态、细胞细胞器和组织重塑的消除。此外,自噬能力在各种疾病状态下发生变化。一系列研究表明,自噬受到严格控制,以维持能量代谢和细胞细胞器及蛋白质周转的稳态平衡。这些研究还表明,该过程通过与 mRNAs 互补碱基配对来转录后调控小非编码 microRNAs 的基因表达。相反,自噬调节 microRNA 的表达。因此,自噬与 microRNA 表达之间的失调会加剧各种疾病的发病机制。在这篇综述中,我们总结了自噬和 microRNA 失调在肝脏疾病过程中的作用,目的是了解 microRNAs 如何修饰关键的自噬效应分子,我们还讨论了这种失调如何影响生理和病理条件。本文可能有助于我们理解肝脏疾病进展的细胞和分子基础,并促进药理学干预策略的发展。

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