Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes.
Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes.
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DOI：
10.1021/pr8004887
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发表时间：
2008-12
影响因子：
4.4
通讯作者：
Falcon-Perez, Juan M.
中科院分区：
文献类型：
--
作者：
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.
关键词：
外泌体构成在内吞区室中形成并由不同细胞类型释放到细胞外环境的纳米尺寸（30-150 nm）囊泡的离散群体。在这项工作中，我们证明了通过电子显微镜，蛋白质印迹和蛋白质组学分析，原代肝细胞分泌外泌体样囊泡含有参与代谢脂蛋白，内源性化合物以及外源性物质的蛋白质。这些新发现有助于提高我们对生物学肝细胞的认识，并可能对肝脏疾病的诊断，预后和治疗具有重要意义。外泌体代表了从各种细胞类型分泌到细胞外介质的离散囊泡群体。它们的蛋白质和脂质组成是在多泡体水平上分选事件的结果，多泡体是整合内吞和分泌途径的中央细胞器。来自不同生物样品的外泌体的表征已经显示存在常见以及细胞类型特异性蛋白。值得注意的是，外泌体的蛋白质含量在病理或应激条件下被改变。肝细胞在机体应激反应中起着重要作用，代谢潜在的有害内源性物质以及外源性物质。在本研究中，我们首次描述和表征了非肿瘤肝细胞中的外泌体分泌，并使用系统的蛋白质组学方法，我们建立了肝细胞来源的外泌体群体的第一个广泛的蛋白质组，这应该有助于我们进一步了解肝功能和鉴定可作为肝脏改变生物标志物的组分。我们的分析鉴定了大量以前在来源于其他细胞类型的外泌体中描述的蛋白质，以及以前在外泌体中未描述的参与代谢脂蛋白、内源性化合物和外源性物质的蛋白质。此外，我们证明了外泌体膜蛋白可以构成一个有趣的工具，表达非外泌体蛋白到外泌体中具有治疗目的。
Exosomes constitute a discrete population of nanometer-sized (30-150 nm) vesicles formed in endocytic compartments and released to the extracellular environment by different cell types. In this work we demonstrated by electron microscopic, western blotting and proteomic analyses that primary hepatocytes secrete exosome-like vesicles containing proteins involved in metabolizing lipoproteins, endogenous compounds as well as xenobiotics. These new findings contribute to improve our knowledge about biology's hepatocyte and may have important diagnostic, prognosis and therapeutic implications in liver diseases 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 first time exosome secretion in non-tumoral hepatocytes, and using 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 non-exosomal proteins into exosomes with therapeutic purposes.
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影响因子：
7
作者：
Ashburner, M;Ball, CA;Yoon, J
通讯作者：
Yoon, J
影响因子：
19.6
作者：
Keller, S.;Rupp, C.;Altevogt, P.
通讯作者：
Altevogt, P.
DOI：
10.1073/pnas.0308413101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Fevrier, B;Vilette, D;Raposo, G
通讯作者：
Raposo, G
影响因子：
24.3
作者：
Admyre, C;Grunewald, J;Gabrielsson, S
通讯作者：
Gabrielsson, S
DOI：
10.1165/rcmb.2003-0238oc
发表时间：
2004-07-01
影响因子：
6.4
作者：
Bard, MP;Hegmans, JP;Lambrecht, BN
通讯作者：
Lambrecht, BN