Conde-Vancells Javier, Rodriguez-Suarez Eva, Embade Nieves, Gil David, Matthiesen Rune, Valle Mikel, Elortza Felix, Lu Shelly C, Mato Jose M, Falcon-Perez Juan M
Metabolomics Unit, CICbioGUNE, CIBERehd, Bizkaia Technology Park, Derio, 48160, Bizkaia, Spain.
J Proteome Res. 2008 Dec;7(12):5157-66. doi: 10.1021/pr8004887.
Exosomes represent a discrete population of vesicles that are secreted from various cell types to the extracellular media. Their protein and lipid composition are a consequence of sorting events at the level of the multivesicular body, a central organelle which integrates endocytic and secretory pathways. Characterization of exosomes from different biological samples has shown the presence of common as well as cell-type specific proteins. Remarkably, the protein content of the exosomes is modified upon pathological or stress conditions. Hepatocytes play a central role in the body response to stress metabolizing potentially harmful endogenous substances as well as xenobiotics. In the present study, we described and characterized for the first time exosome secretion in nontumoral hepatocytes, and with the use of a systematic proteomic approach, we establish the first extensive proteome of a hepatocyte-derived exosome population which should be useful in furthering our understanding of the hepatic function and in the identification of components that may serve as biomarkers for hepatic alterations. Our analysis identifies a significant number of proteins previously described among exosomes derived from others cell types as well as proteins involved in metabolizing lipoproteins, endogenous compounds and xenobiotics, not previously described in exosomes. Furthermore, we demonstrated that exosomal membrane proteins can constitute an interesting tool to express nonexosomal proteins into exosomes with therapeutic purposes.
外泌体是一类从各种细胞类型分泌到细胞外介质中的离散囊泡群体。它们的蛋白质和脂质组成是多泡体水平上分选事件的结果，多泡体是一个整合内吞和分泌途径的中心细胞器。对来自不同生物样品的外泌体的表征显示存在共同的以及细胞类型特异性的蛋白质。值得注意的是，外泌体的蛋白质含量在病理或应激条件下会发生改变。肝细胞在机体对压力的反应中起着核心作用，它能代谢潜在有害的内源性物质以及外源性物质。在本研究中，我们首次描述并表征了非肿瘤性肝细胞中外泌体的分泌情况，并通过系统的蛋白质组学方法，建立了首个广泛的肝细胞衍生外泌体群体蛋白质组，这将有助于加深我们对肝功能的理解，并有助于识别可能作为肝脏改变生物标志物的成分。我们的分析鉴定出大量先前在源自其他细胞类型的外泌体中描述过的蛋白质，以及参与脂蛋白、内源性化合物和外源性物质代谢的蛋白质，这些蛋白质以前在外泌体中未曾描述过。此外，我们证明外泌体膜蛋白可以构成一种有趣的工具，用于将非外泌体蛋白表达于外泌体中以达到治疗目的。
