Traumatic brain injury increases levels of miR-21 in extracellular vesicles: implications for neuroinflammation.
Traumatic brain injury increases levels of miR-21 in extracellular vesicles: implications for neuroinflammation.
复制标题
DOI：
10.1002/2211-5463.12092
复制
发表时间：
2016-08
期刊：
影响因子：
2.6
通讯作者：
Yelamanchili SV
中科院分区：
文献类型：
--
作者：
Harrison EB;Hochfelder CG;Lamberty BG;Meays BM;Morsey BM;Kelso ML;Fox HS;Yelamanchili SV
创伤性脑损伤（TBI）是一个重要的健康问题，有效的治疗策略仍然难以捉摸。了解复杂的多细胞反应TBI可能提供新的干预途径。在TBI的背景下，细胞间通讯至关重要。TBI中细胞间通讯的一种相对未探索的形式是细胞外囊泡（EV）。这些膜结合囊泡可以在细胞之间携带许多不同类型的货物。最近，EV中的miRNA已被证明介导神经炎症和神经元损伤。为了探索EV相关miRNA在TBI中的作用，我们从受伤小鼠和对照小鼠的大脑中分离EV，从大脑EV中纯化RNA，并进行miRNA测序。我们发现，随着损伤的发生，miR-212的表达降低，而miR-21、miR-146、miR-7a和miR-7 b的表达显著增加，其中miR-21在不同条件下的变化最大。大脑中miR-21的表达主要定位于病变部位附近的神经元。有趣的是，与这些表达miR-21的神经元相邻的是活化的小胶质细胞。EV中miR-21的增加与神经元中miR-21的升高同时发生，表明miR-21作为潜在的EV货物从神经元分泌。因此，这项研究揭示了一个新的潜在的细胞间通讯机制，以前没有在TBI中描述。
Traumatic brain injury (TBI) is an important health concern and effective treatment strategies remain elusive. Understanding the complex multicellular response to TBI may provide new avenues for intervention. In the context of TBI, cell–cell communication is critical. One relatively unexplored form of cell–cell communication in TBI is extracellular vesicles (EVs). These membrane‐bound vesicles can carry many different types of cargo between cells. Recently, miRNA in EVs have been shown to mediate neuroinflammation and neuronal injury. To explore the role of EV‐associated miRNA in TBI, we isolated EVs from the brain of injured mice and controls, purified RNA from brain EVs, and performed miRNA sequencing. We found that the expression of miR‐212 decreased, while miR‐21, miR‐146, miR‐7a, and miR‐7b were significantly increased with injury, with miR‐21 showing the largest change between conditions. The expression of miR‐21 in the brain was primarily localized to neurons near the lesion site. Interestingly, adjacent to these miR‐21‐expressing neurons were activated microglia. The concurrent increase in miR‐21 in EVs with the elevation of miR‐21 in neurons, suggests that miR‐21 is secreted from neurons as potential EV cargo. Thus, this study reveals a new potential mechanism of cell–cell communication not previously described in TBI.