Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
Biomolecules. 2023 Jan 24;13(2):222. doi: 10.3390/biom13020222.
Most eukaryotic cells, including hepatocytes, secrete exosomes into the extracellular space, which are vesicles facilitating horizontal cell-to-cell communication of molecular signals and physiological cues. The molecular cues for cellular functions are carried by exosomes via specific mRNAs, microRNAs, and proteins. Exosomes released by liver cells are a vital part of biomolecular communication in liver diseases. Importantly, exosomes play a critical role in mediating alcohol-associated liver disease (ALD) and are potential biomarkers for ALD. Moreover, alcohol exposure itself promotes exosome biogenesis and release from the livers of humans and rodent models. However, the mechanisms by which alcohol promotes exosome biogenesis in hepatocytes are still unclear. Of note, alcohol exposure leads to liver injury by modulating various cellular processes, including autophagy, ER stress, oxidative stress, and epigenetics. Evidence suggests that there is a link between each of these processes with exosome biogenesis. The aim of this review article is to discuss the interplay between ethanol exposure and these altered cellular processes in promoting hepatocyte exosome biogenesis and release. Based on the available literature, we summarize and discuss the potential mechanisms by which ethanol induces exosome release from hepatocytes, which in turn leads to the progression of ALD.
大多数真核细胞，包括肝细胞，都会将外泌体分泌到细胞外空间，这些囊泡促进分子信号和生理信号的水平细胞间通讯。外泌体通过特定的 mRNAs、microRNAs 和蛋白质携带细胞功能的分子线索。肝细胞释放的外泌体是肝脏疾病中生物分子通讯的重要组成部分。重要的是，外泌体在介导酒精相关肝病 (ALD) 中发挥着关键作用，并且是 ALD 的潜在生物标志物。此外，酒精暴露本身会促进人类和啮齿动物模型肝脏中外泌体的生物发生和释放。然而，酒精促进肝细胞中外泌体生物发生的机制尚不清楚。值得注意的是，酒精暴露通过调节自噬、内质网应激、氧化应激和表观遗传学等各种细胞过程导致肝损伤。有证据表明，这些过程中的每一个都与外泌体生物发生有关。本文综述的目的是讨论乙醇暴露与这些改变的细胞过程之间的相互作用，以促进肝细胞中外泌体的生物发生和释放。根据现有文献，我们总结并讨论了乙醇诱导肝细胞释放外泌体的潜在机制，进而导致 ALD 的进展。
