MiR-30a Positively Regulates the Inflammatory Response of Microglia in Experimental Autoimmune Encephalomyelitis
MiR-30a Positively Regulates the Inflammatory Response of Microglia in Experimental Autoimmune Encephalomyelitis
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MiR-30a 正向调节实验性自身免疫性脑脊髓炎中小胶质细胞的炎症反应
DOI：
10.1007/s12264-017-0153-y
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发表时间：
2017-12-01
影响因子：
5.6
通讯作者：
Cao, Li
中科院分区：
文献类型：
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作者：
Fang, Xue;Sun, Dingya;Cao, Li
多发性硬化（MS）是一种典型的中枢神经系统炎性脱髓鞘疾病。小胶质细胞是中枢神经系统中主要的常驻免疫细胞，与MS的发病机制密切相关。在本研究中，我们发现miR-30 a在MS患者慢性活动性病变中的斑马鱼样小胶质细胞以及实验性自身免疫性脑脊髓炎（EAE）小鼠慢性期的小胶质细胞中高表达。过表达miR-30 a的小鼠小胶质细胞条件培养上清可促进少突胶质前体细胞（oligodendrocyte precursor cells，OPCs）凋亡，抑制OPCs分化;在体内，过表达miR-30 a的小胶质细胞移植可加重EAE的进展。在原代培养的小鼠小胶质细胞中的过表达和敲低实验表明，miR-30 a增加了促炎性因子IL-1β和iNOS的表达，同时抑制了Ym-1和CD 206的表达。从机制上讲，miR-30 a抑制Ppargc 1b的表达，Ppargc 1b是过氧化物酶体增殖物激活受体γ的共激活剂，导致促炎作用。我们的工作表明，miR-30 a是小胶质细胞炎症反应的重要调节因子，可能是CNS中MS等炎症性疾病的有希望的治疗靶点。
Multiple sclerosis (MS) is a classical inflammatory demyelinating disease of the central nervous system (CNS). Microglia are the main resident immune cells in the CNS and are closely associated with the pathogenesis of MS. In the present study, we found that miR-30a was highly expressed in jellyfish-like microglia in chronic active lesions of MS patients, as well as in the microglia of mice with experimental autoimmune encephalomyelitis (EAE) at the chronic phase.In vitro, the conditioned supernatant of mouse microglia overexpressing miR-30a promoted the apoptosis of oligodendrocyte precursor cells (OPCs), and inhibited OPC differentiation.In vivo, overexpressing miR-30a in transplanted microglia exacerbated the progression of EAE. Overexpression and knock-down experiments in primary cultured mouse microglia showed that miR-30a increased the expression of IL-1β and iNOS, which are pro-inflammatory, while inhibiting the expression of Ym-1 and CD206. Mechanistically, miR-30a inhibited the expression of Ppargc1b, which is the co-activator of peroxisome proliferator-activated receptor gamma, resulting in pro-inflammatory effects. Our work shows that miR-30a is an important regulator of the inflammatory response in microglia, and may be a promising therapeutic target for inflammatory diseases like MS in the CNS.