摘要
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 mi R-30 a 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-30 a promoted the apoptosis of oligodendrocyte precursor cells（OPCs）, and inhibited OPC differentiation. In vivo, overexpressing miR-30 a in transplanted microglia exacerbated the progression of EAE.Overexpression and knock-down experiments in primary cultured mouse microglia showed that mi R-30 a increased the expression of IL-1 b and i NOS, which are pro-inflammatory, while inhibiting the expression of Ym-1 and CD206.Mechanistically, mi R-30 a inhibited the expression of Ppargc1 b, which is the co-activator of peroxisome proliferator-activated receptor gamma, resulting in pro-inflammatory effects. Our work shows that mi R-30 a 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.
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 mi R-30 a 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-30 a promoted the apoptosis of oligodendrocyte precursor cells（OPCs）, and inhibited OPC differentiation. In vivo, overexpressing miR-30 a in transplanted microglia exacerbated the progression of EAE.Overexpression and knock-down experiments in primary cultured mouse microglia showed that mi R-30 a increased the expression of IL-1 b and i NOS, which are pro-inflammatory, while inhibiting the expression of Ym-1 and CD206.Mechanistically, mi R-30 a inhibited the expression of Ppargc1 b, which is the co-activator of peroxisome proliferator-activated receptor gamma, resulting in pro-inflammatory effects. Our work shows that mi R-30 a 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.
基金
supported by the International Cooperation and Exchange of the National Natural Science Foundation of China(81461138035)
the National Natural Science Foundation of China(81371326,31371068,and 31571066)
the National Key Research and Development Program of China(2016YFA0100802)
