Exosome proteins associated with neural function.

Exosomes derived from endothelial cells and Schwann cells have been employed as novel treatments of neurological diseases, including peripheral neuropathy. Exosomal cargo plays a critical role in mediating recipient cell function. In this study, we thus performed a comprehensive proteomic analysis of exosomes derived from healthy mouse dermal microvascular endothelial cells (EC-Exo) and healthy mouse Schwann cells (SC-Exo). We detected 1,817and 1,579 proteins in EC-Exo and SC-Exo, respectively. Among them, 1506 proteins were present in both EC-Exo and SC-Exo, while 311 and 73 proteins were detected only in EC-Exo and SC-Exo, respectively. Bioinformatic analysis revealed that EC-Exo enriched proteins were involved in neurovascular function, while SC-Exo enriched proteins were related to lipid metabolism. Western blot analysis of 14 enriched proteins revealed that EC-Exo contained proteins involved in mediating endothelial function such as delta-like 4 (DLL4) and endothelial NOS (NOS3), whereas SC-Exo had proteins involved in mediating glial function such as apolipoprotein A-I (APOA1) and phospholipid transfer protein (PLTP). Collectively, the present study identifies differences in the cargo protein profiles of EC-Exo and SC-Exo, thus providing new molecular insights into their biological functions for the treatment of peripheral neuropathy.

内皮细胞（endothelial cells）与雪旺细胞（Schwann cells）来源的外泌体已被用作包括周围神经病在内的神经系统疾病的新型治疗策略。外泌体载荷（exosomal cargo）在介导受体细胞功能过程中发挥关键作用。本研究遂对健康小鼠真皮微血管内皮细胞来源的外泌体（EC-Exo）与健康小鼠雪旺细胞来源的外泌体（SC-Exo）开展了全面的蛋白质组学分析。我们分别在EC-Exo与SC-Exo中检测到1817和1579种蛋白质。其中，1506种蛋白质同时存在于EC-Exo与SC-Exo中，而仅在EC-Exo中检出的蛋白质有311种，仅在SC-Exo中检出的则有73种。生物信息学分析显示，EC-Exo富集的蛋白质参与神经血管功能，而SC-Exo富集的蛋白质则与脂质代谢相关。对14种富集蛋白质的蛋白质印迹（Western blot）分析结果表明，EC-Exo含有介导内皮细胞功能的相关蛋白质，如delta样蛋白4（delta-like 4, DLL4）和内皮型一氧化氮合酶（endothelial NOS, NOS3）；而SC-Exo则包含介导胶质细胞功能的蛋白质，如载脂蛋白A-I（apolipoprotein A-I, APOA1）和磷脂转移蛋白（phospholipid transfer protein, PLTP）。综上，本研究明确了EC-Exo与SC-Exo在外泌体载荷蛋白质谱上的差异，为二者用于治疗周围神经病的生物学功能提供了全新的分子层面阐释。