Yang Jun, Tang Xiaolei, Chen Liang, Hu Junjie, Li Shan, Yuan Ming, Tian Xianxiang, Qiu Zhenpeng
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic of China.
Translational Medicine Center of the Second Affiliated Hospital of Wannan Medical College, Wuhu, 241002, People's Republic of China.
Curr Med Chem. 2024 Jan 30. doi: 10.2174/0109298673276581231210170332.
Nonalcoholic fatty liver disease (NAFLD) is of global concern due to its high prevalence worldwide. NAFLD, as one of the most common causes of liver function abnormalities, is associated with obesity, insulin resistance, and type 2 diabetes mellitus, and there are no medications available to treat NAFLD. Extracellular vesicles (EVs) are nanosized, membrane-bound vesicles that deliver biomolecules between cells. Exosomes are a subtype of EVs that mediate intercellular communication by delivering proteins and RNAs. MicroRNAs (miRNAs) are a highly conserved class of small tissue-specific non-coding RNAs that influence the expression of many functionally interacting genes. Hepatic-derived exosomal miRNAs are tightly associated with NAFLD occurrence and progression through multiple mechanisms. In addition, the characterization of miRNAs suggests that they may serve as multifunctional biomarkers for NAFLD, be used as clinical therapeutic targets for NAFLD, and be significant predictors of patient prognosis. Here, we review recent advances in the regulation and function of exosome-derived miRNAs in NAFLD, focusing on miRNAs specifically expressed or enriched in hepatocytes (HCs), hepatic macrophages, hepatic stellate cells (HSCs), and other immune cells in the liver. Finally, we discuss future research directions on exosomal miRNAs as biomarkers for NAFLD's diagnosis and clinical therapeutic targets.
非酒精性脂肪性肝病（NAFLD）因其在全球的高患病率而受到全球关注。NAFLD作为肝功能异常最常见的原因之一，与肥胖、胰岛素抵抗和2型糖尿病相关，且尚无治疗NAFLD的药物。细胞外囊泡（EVs）是纳米大小的膜结合囊泡，可在细胞间传递生物分子。外泌体是EVs的一种亚型，通过传递蛋白质和RNA介导细胞间通讯。微小RNA（miRNAs）是一类高度保守的小组织特异性非编码RNA，可影响许多功能相互作用基因的表达。肝脏来源的外泌体miRNAs通过多种机制与NAFLD的发生和进展密切相关。此外，miRNAs的特性表明它们可能作为NAFLD的多功能生物标志物，用作NAFLD的临床治疗靶点，并成为患者预后的重要预测指标。在此，我们综述了外泌体来源的miRNAs在NAFLD中的调控和功能的最新进展，重点关注在肝细胞（HCs）、肝巨噬细胞、肝星状细胞（HSCs）和肝脏中其他免疫细胞中特异性表达或富集的miRNAs。最后，我们讨论了外泌体miRNAs作为NAFLD诊断生物标志物和临床治疗靶点的未来研究方向。
