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...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.展开更多
AIM: To determine if mir-30 d inhibits the autophagy response to Helicobacter pylori(H. pylori) invasion and increases H. pylori intracellular survival.METHODS: The expression of mir-30 d was detected by quantitative ...AIM: To determine if mir-30 d inhibits the autophagy response to Helicobacter pylori(H. pylori) invasion and increases H. pylori intracellular survival.METHODS: The expression of mir-30 d was detected by quantitative polymerase chain reaction(PCR), and autophagy level was examined by transmission electron microscopy, western blot, and GFP-LC3 puncta assay in human AGS cells and GES-1 cells. Luciferase reporter assay was applied to confirm the specificity of mir-30 d regulation on the expression of several core molecules involved in autophagy pathway. The expression of multiple core proteins were analyzed at both the m RNA and protein level, and the intracellular survival of H. pylori after different treatments was detected by gentamicin protection assay.RESULTS: Autophagy level was increased in AGS and GES-1 cells in response to H. pylori infection, which was accompanied by upregulation of mir-30 d expression(P < 0.05, vs no H. pylori infection). In the two gastric epithelial cell lines, mimic mir-30 d was found to repress the autophagy process, whereas mir-30 d inhibitor increased autophagy responseto H. pylori invasion. mir-30 d mimic decreased the luciferase activity of wild type reporter plasmids carrying the 3′ untranslated region(UTR) of all five tested genes(ATG2B, ATG5, ATG12, BECN1, and BNIP3L), whereas it had no effect on the mutant reporter plasmids. These five genes are core genes of autophagy pathway, and their expression was reduced significantly after mir-30 d mimic transfection(P < 0.05, vs control cells without mir-30 d mimic treatment). Mir-30 d mimic transfection and direct inhibition of autophagy increased the intracellular survival of H. pylori in AGS cells.CONCLUSION: Mir-30 d increases intracellular survival of H. pylori in gastric epithelial cells through inhibition of multiple core proteins in the autophagy pathway.展开更多
目的分析microRNA-30a(miR-30a)在慢性肾衰竭患者透析前后血清中的表达差异,评价其在评估慢性肾衰竭血液透析效果中的作用。方法选取2012年10月至2013年12月本科收治的慢性肾衰竭患者40例,分别在患者透析前后采血并获得血清样本,采用mir...目的分析microRNA-30a(miR-30a)在慢性肾衰竭患者透析前后血清中的表达差异,评价其在评估慢性肾衰竭血液透析效果中的作用。方法选取2012年10月至2013年12月本科收治的慢性肾衰竭患者40例,分别在患者透析前后采血并获得血清样本,采用mirV ana PARIS Kit提取血清样本中总RNA,利用qRT-PCR法检测miR-30a的表达,临床生化检测患者透析前后血清中肌酐(Cr)、尿素氮(Ur)及β2微球蛋白(β2-MG)的含量,表达值行曼-惠特尼U检验,工作特征曲线(ROC curve)评估miR-30a在慢性肾衰竭患者透析效果中的价值。结果 miR-30a、Ur和β2-MG在慢性肾衰竭患者透析后的表达显著低于透析前(P<0.05,P<0.01),ROC curve显示在患者透析后miR-30a的表达低于透析前0.25倍以上时患者可获得较好的透析效果。结论 miR-30a可作为一种潜在的评估慢性肾衰竭血液透析效果的生物标志物。展开更多
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)
文摘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 National Natural Science Fund from China,No.81260326
文摘AIM: To determine if mir-30 d inhibits the autophagy response to Helicobacter pylori(H. pylori) invasion and increases H. pylori intracellular survival.METHODS: The expression of mir-30 d was detected by quantitative polymerase chain reaction(PCR), and autophagy level was examined by transmission electron microscopy, western blot, and GFP-LC3 puncta assay in human AGS cells and GES-1 cells. Luciferase reporter assay was applied to confirm the specificity of mir-30 d regulation on the expression of several core molecules involved in autophagy pathway. The expression of multiple core proteins were analyzed at both the m RNA and protein level, and the intracellular survival of H. pylori after different treatments was detected by gentamicin protection assay.RESULTS: Autophagy level was increased in AGS and GES-1 cells in response to H. pylori infection, which was accompanied by upregulation of mir-30 d expression(P < 0.05, vs no H. pylori infection). In the two gastric epithelial cell lines, mimic mir-30 d was found to repress the autophagy process, whereas mir-30 d inhibitor increased autophagy responseto H. pylori invasion. mir-30 d mimic decreased the luciferase activity of wild type reporter plasmids carrying the 3′ untranslated region(UTR) of all five tested genes(ATG2B, ATG5, ATG12, BECN1, and BNIP3L), whereas it had no effect on the mutant reporter plasmids. These five genes are core genes of autophagy pathway, and their expression was reduced significantly after mir-30 d mimic transfection(P < 0.05, vs control cells without mir-30 d mimic treatment). Mir-30 d mimic transfection and direct inhibition of autophagy increased the intracellular survival of H. pylori in AGS cells.CONCLUSION: Mir-30 d increases intracellular survival of H. pylori in gastric epithelial cells through inhibition of multiple core proteins in the autophagy pathway.
文摘目的分析microRNA-30a(miR-30a)在慢性肾衰竭患者透析前后血清中的表达差异,评价其在评估慢性肾衰竭血液透析效果中的作用。方法选取2012年10月至2013年12月本科收治的慢性肾衰竭患者40例,分别在患者透析前后采血并获得血清样本,采用mirV ana PARIS Kit提取血清样本中总RNA,利用qRT-PCR法检测miR-30a的表达,临床生化检测患者透析前后血清中肌酐(Cr)、尿素氮(Ur)及β2微球蛋白(β2-MG)的含量,表达值行曼-惠特尼U检验,工作特征曲线(ROC curve)评估miR-30a在慢性肾衰竭患者透析效果中的价值。结果 miR-30a、Ur和β2-MG在慢性肾衰竭患者透析后的表达显著低于透析前(P<0.05,P<0.01),ROC curve显示在患者透析后miR-30a的表达低于透析前0.25倍以上时患者可获得较好的透析效果。结论 miR-30a可作为一种潜在的评估慢性肾衰竭血液透析效果的生物标志物。
