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TLR3激活协同干扰素α抑制小鼠海马神经元DISC1表达

Toll-like receptor 3 activation combined with INFαinhibits the expression of DISC1 in hippocampal neurons of mice
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摘要 目的研究TLR3激活对小鼠海马神经元的精神分裂症断裂基因1(DISC1)表达的影响。方法分离培养C57BL/6J小鼠E18海马神经元,给予1μg/mL polyI:C或/和100 IU/mL mIFNα处理细胞24 h后,用RT-qPCR、免疫细胞化学和Western blot方法检测DISC1 mRNA和蛋白的表达,并检测p38丝裂原活化蛋白激酶(p38 MAPK)、信号传导和转录激活因子1(STAT1)及糖原合成激酶3β(GSK-3β)的磷酸化。结果相比对照组,polyI:C组和IFNα组DISC1 mRNA及蛋白水平无明显变化,而共刺激(IFNα+polyI:C)组DISC1表达显著下降(P<0.05)。此外,polyI:C和共刺激组p38 MAPK磷酸化水平增加(P<0.05),且IFNα和共刺激组STAT1磷酸化水平亦显著升高(P<0.05),而GSK-3β磷酸化水平无变化。结论外源性IFNα协同TLR3激活可部分通过p38 MAPK和JAK/STAT1信号通路抑制DISC1的表达。 Objective To explore the effect of Toll-like receptor 3(TLR3)activation on the expression of neuronal disrupted-in-schizophrenia 1(DISC1).Methods C57BL/6J mouse hippocampal neurons were incubated with polyI:C(1μg/mL)or/and mIFNα(100 IU/mL)for 24 hrs.DISC1 mRNA and protein were detected by quantitive RT-PCR,immuno-cytochemistry staining and Western blot.The expression of STAT1,phospho-STAT1,p38 MAPK,phospho-p38 MAPK,GSK-3β,and phospho-GSK-3βwas also detected by Western blot.Results Comparing with control group,the mRNA and protein expression of DISC1 in polyI:C group and IFNαgroup didn't show any changes,but significantly decreased with the co-stimulation by polyI:C and IFNα(P<0.05).In addition,the phosphorylation of STAT1 was significantly increased in both IFNαgroup and co-stimulation group(P<0.05)and the phosphorylation of p38 MAPK was elevated in polyI:C group and co-stimulation group(P<0.05).The expression of GSK-3βand phospho-GSK-3βhad no changes.Conclusions The combined stimulations of IFNαand TLR3 activation may inhibit the expression of DISC1 potentially through JAK/STAT1 and p38 MAPK signaling pathways.
作者 姚景宏 李加欢 刘子建 YAO Jing-hong;LI Jia-huan;LIU Zi-jian(Department of Infectious Diseases,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022;Department of Anatomy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)
出处 《基础医学与临床》 2022年第12期1855-1860,共6页 Basic and Clinical Medicine
基金 中国肝炎防治基金会天晴肝病研究基金(TQGB20200137)。
关键词 精神分裂症断裂基因1 TOLL样受体3 干扰素Α 信号传导和转录激活因子1 P38丝裂原活化蛋白激酶 disrupted-in-schizophrenia 1 Toll-like receptor 3 interferonα STAT1 p38 MAPK
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