Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis.
Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis.
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小胶质细胞来源的外泌体通过miR-615-5p/MYRF轴调节髓磷脂再生。
DOI：
10.1186/s12974-024-03019-5
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发表时间：
2024-01-22
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
脱髓鞘和髓鞘再生失败在中枢神经系统（CNS）特征的一些神经系统疾病。脱髓鞘疾病的自发性髓鞘再生是有限的，因为通常在脱髓鞘病变中大量存在的少突胶质前体细胞（OPCs）大多不能分化为少突胶质细胞，即中枢神经系统的髓鞘细胞。除了OPCs外，病变还聚集了大量活化的常驻小胶质细胞/浸润的巨噬细胞；然而，小胶质细胞/巨噬细胞与OPCs之间相互作用的机制和潜在作用尚不清楚。在这里，我们从活化的小胶质细胞中生成外泌体的转录谱，发现miR-615-5p升高。miR-615-5p结合髓鞘调节因子（MYRF）的3'UTR，髓鞘调节因子是在少突胶质细胞谱系细胞中表达的关键髓鞘转录因子。在机制上，来自活化小胶质细胞的外泌体将miR-615-5p转移到OPC上，直接结合MYRF并抑制OPC成熟。此外，在实验性自身免疫性脑脊髓炎（EAE）和铜酮（CPZ）诱导的脱髓鞘模型（多发性硬化症经典小鼠模型）中，检测了表达miR-615-5p海绵的AAV在小胶质细胞中的作用。miR-615-5p海绵可有效缓解疾病进展，促进骨髓鞘再生。本研究确定miR-615-5p/MYRF作为脱髓鞘疾病治疗的新靶点。在线版本包含补充材料，可在10.1186/s12974-024-03019-5获得。
Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3′UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases. The online version contains supplementary material available at 10.1186/s12974-024-03019-5.
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影响因子：
3.3
作者：
Paton, Kelly F.;Hong, Sheein;Biggerstaff, Andrew;Kivell, Bronwyn M.
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
15.1
作者：
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通讯作者：
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影响因子：
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