Washington Alexander M, Kostallari Enis
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota.
Semin Liver Dis. 2025 Jun;45(2):167-179. doi: 10.1055/a-2494-2233. Epub 2024 Dec 3.
Progression of liver disease is dependent on intercellular signaling, including those mediated by extracellular vesicles (EVs). Within these EVs, microRNAs (miRNAs) are packaged to selectively silence gene expression in recipient cells for upregulating or downregulating a specific pathway. Injured hepatocytes secrete EV-associated miRNAs which can be taken up by liver sinusoidal endothelial cells, immune cells, hepatic stellate cells, and other cell types. In addition, these recipient cells will secrete their own EV-associated miRNAs to propagate a response throughout the tissue and the circulation. In this review, we comment on the implications of EV-miRNAs in the progression of alcohol-associated liver disease, metabolic dysfunction-associated steatohepatitis, viral and parasitic infections, liver fibrosis, and liver malignancies. We summarize how circulating miRNAs can be used as biomarkers and the potential of utilizing EVs and miRNAs as therapeutic methods to treat liver disease.
肝脏疾病的进展取决于细胞间信号传导,包括由细胞外囊泡(EVs)介导的信号传导。在这些细胞外囊泡中,微小RNA(miRNAs)被包裹起来,以选择性地沉默受体细胞中的基因表达,从而上调或下调特定途径。受损的肝细胞分泌与细胞外囊泡相关的微小RNA,这些微小RNA可被肝窦内皮细胞、免疫细胞、肝星状细胞和其他细胞类型摄取。此外,这些受体细胞会分泌它们自己的与细胞外囊泡相关的微小RNA,以在整个组织和循环中传播反应。在这篇综述中,我们评论了细胞外囊泡微小RNA在酒精性肝病、代谢功能障碍相关脂肪性肝炎、病毒和寄生虫感染、肝纤维化以及肝脏恶性肿瘤进展中的意义。我们总结了循环微小RNA如何用作生物标志物,以及利用细胞外囊泡和微小RNA作为治疗肝病的治疗方法的潜力。