Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis.
Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR-155 in Experimental Autoimmune Encephalomyelitis.
复制标题
DOI：
10.1155/2021/5753452
复制
发表时间：
2021
影响因子：
--
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Liu X;Ma J;Ding G;Gong Q;Wang Y;Yu H;Cheng X
活化的小胶质细胞被认为是中枢神经系统（CNS）脱髓鞘疾病中神经炎症环境的主要介质。激活的小胶质细胞主要极化为M1型，具有促进炎症和脱髓鞘的作用。但小胶质细胞极化为M2型的比例相对较低，不能充分发挥抗炎、抗脱髓鞘的作用。我们前期研究发现黄芪多糖（Astragalus polysaccharides， APS）具有免疫调节作用，可抑制实验性自身免疫性脑脊髓炎（EAE）的神经炎症和脱髓鞘，EAE是中枢神经系统脱髓鞘疾病的经典动物模型。在本研究中，我们发现APS对EAE小鼠有治疗作用。在体内和体外通过抑制小胶质细胞向m1样表型极化，促进小胶质细胞向m2样表型极化，恢复小胶质细胞平衡。miR-155是调节小胶质细胞极化的关键因子。我们发现黄芪多糖在体内和体外均能抑制miR-155的表达水平。此外，我们进行了转染过表达和阻断实验。结果表明，miR-155介导了小胶质细胞M1/M2表型的极化，而miR-155的选择性抑制剂减弱了APS对小胶质细胞M1表型的抑制作用，消除了APS对小胶质细胞M2表型的促进作用。小胶质细胞极化为M1型后可分泌IL-1α、TNF-α和C1q，诱导A1神经毒性星形胶质细胞活化，进一步加重神经炎症和脱髓鞘。APS可减少活化小胶质细胞分泌IL-1α、TNF-α和C1q，从而抑制A1神经毒性星形胶质细胞的形成。综上所述，我们的研究表明，APS通过抑制miR-155调节小胶质细胞从M1表型向M2表型的极化，减少炎症因子的分泌，抑制神经毒性星形胶质细胞的激活，从而有效治疗EAE。
Activated microglia is considered to be major mediators of the neuroinflammatory environment in demyelinating diseases of the central nervous system (CNS). Activated microglia are mainly polarized into M1 type, which plays a role in promoting inflammation and demyelinating. However, the proportion of microglia polarized into M2 type is relatively low, which cannot fully play the role of anti-inflammatory and resistance to demyelinating. Our previous study found that Astragalus polysaccharides (APS) has an immunomodulatory effect and can inhibit neuroinflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), which is a classic animal model of CNS demyelinating disease. In this study, we found that APS was effective in treating EAE mice. It restored microglia balance by inhibiting the polarization of microglia to M1-like phenotype and promoting the polarization of microglia to M2-like phenotype in vivo and in vitro. miR-155 is a key factor in regulating microglia polarization. We found that APS could inhibit the expression level of miR-155 in vivo and in vitro. Furthermore, we performed transfection overexpression and blocking experiments. The results showed that miR-155 mediated the polarization of microglia M1/M2 phenotype, while the selective inhibitor of miR-155 attenuated the inhibition of APS on microglia M1 phenotype and eliminated the promotion of APS on microglia M2 phenotype. Microglia can secrete IL-1α, TNF-α, and C1q after polarizing into M1 type and induce the activation of A1 neurotoxic astrocytes, further aggravating neuroinflammation and demyelination. APS reduced the secretion of IL-1α, TNF-α, and C1q by activated microglia, thus inhibited the formation of A1 neurotoxic astrocytes. In summary, our study suggests that APS regulates the polarization of microglia from M1 to M2 phenotype by inhibiting the miR-155, reduces the secretion of inflammatory factors, and inhibits the activation of neurotoxic astrocytes, thus effectively treating EAE.
登录
查看更多内容
影响因子：
3.3
作者：
Dickey LL;Hanley TM;Huffaker TB;Ramstead AG;O'Connell RM;Lane TE
通讯作者：
Lane TE
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
Radix Astragali（Astragalus膜的根部山地）沿其价值链的质量控制。
影响因子：
5.6
作者：
Bi Y;Bao H;Zhang C;Yao R;Li M
通讯作者：
Li M
影响因子：
3
作者：
Colton, Carol A.;Wilcock, Donna M.
通讯作者：
Wilcock, Donna M.
影响因子：
6.4
作者：
Cardoso, Ana L.;Guedes, Joana R.;Pedroso de Lima, Maria C.
通讯作者：
Pedroso de Lima, Maria C.