高级检索

    IGF2BP2激活JAK2/STAT3轴促进缺血性脑卒中的炎性因子激活

    IGF2BP2 activates JAK2/STAT3 axis to promote the activation of inflammatory factors in ischemic stroke

      摘要
    • 摘要:
      目的： 探明IGF2BP2激活JAK2/STAT3轴促进缺血性脑卒中（CIS）的炎性因子激活的分子机制。
      方法： 通过GEO数据库数据，筛选脑卒中相关分子。收集60例CIS病人外周血样本，ELISA检测其IGF2BP2的表达情况。同时构建CIS动物模型，分为空白对照组（NC组）、缺血性脑卒中组（CIS组）和缺血性脑卒中 + IGF2BP2抑制剂CWI1-2组（CIS + CWI1-2组）。免疫荧光检测神经元标记物NeuN和炎性小体NLRP3的表达。ELISA实验检测各组中白细胞介素（IL）-6、肿瘤坏死因子-a、IL-1β、IL-8和STAT3的表达，Western blotting实验检测各组中JAK2、Caspase-1、STAT3的表达。
      结果： 基于GEO中GSE16561和GSE22255数据集显示，IGFBP2在CIS病人（n = 59例）中过表达（P ＜ 0.05）。 60例CIS病人中高表达IGFBP2组的高脂血症占比较低表达IGFBP2高（P ＜ 0.05）。动物模型结果显示，相较于NC组，CIS组中脑梗死面积增大，而相较于CIS组，CIS + CWI1-2组的梗死面积减少（F = 1303.00，MS组内 = 384.500，P ＜ 0.01）。免疫荧光结果提示，沉默IGFBP2后NeuN的表达恢复，而NLRP3表达下降（P ＜ 0.05）。ELISA结果显示，沉默IGFBP2可以降低中IL-6、肿瘤坏死因子-a、IL-1β、IL-8和STAT3的表达（P ＜ 0.05）。Western blotting结果显示，沉默IGHFBP2降低了JAK2、Caspase-1、NLRP3和STAT3的蛋白表达水平（P ＜ 0.05）。
      结论： IGF2BP2激活JAK2/STAT3轴促进CIS的炎性因子激活。

       

      Abstract:
      Objective To investigate the molecular mechanism of IGF2BP2 activation of JAK2/STAT3 axis to promote the activation of inflammatory factors in cerebral ischemic stroke (CIS).
      Methods Stroke-related molecules were screened by GEO database data. Peripheral blood samples from 60 patients with ischemic stroke were collected, and the expression of IGF2BP2 in peripheral blood samples was detected by ELISA. The ischemic stroke animal model was constructed and divided into blank control group ( NC group), ischemic stroke group (CIS group) and ischemic stroke + IGF2BP2 inhibitor CWI1-2 group (CIS + CWI1-2 group). The expressions of NeuN and NLRP3 were assessed by immunofluorescence. The expressions of interleukin(IL)-6, tumor necrosis factor-a (TNF-α), IL-1β, IL-8 and STAT3 in each group were detected by ELISA, and the expressions of JAK2, cleaved Caspase-1 (C-Caspase-1) and STAT3 in each group were detected by Western blotting.
      Results Based on the GSE16561 and GSE22255 data sets in GEO, IGF2BP2 was overexpressed in CIS patients (n = 59 cases) (P ＜ 0.05). The 60 CIS patients showed that the proportion of hyperlipidemia in the group with high expression of IGF2BP2 was higher than that in the group with low expression of IGFBP2 (P ＜ 0.05). The results of animal model showed that compared with the NC group, the infarct size in CIS group was increased, while that in CIS + CWI1-2 group was decreased (F = 1303.00, MSwithin = 384.500, P ＜ 0.01). Immunofluorescence results indicated that NeuN expression recovered after IGF2BP2 silencing, while NLRP3 expression decreased (P ＜ 0.05). ELISA results showed that silenced IGFBP2 could decrease the expression of IL-6, tumor necrosis factor-a, IL-1β, IL-8 and STAT3 (P ＜ 0.05). Western blotting results showed that silencing IGHFBP2 decreased the protein levels of JAK2, Caspase-1, NLRP3 and STAT3 (P ＜ 0.05).
      Conclusion IGF2BP2 promotes inflammatory factor activation in cerebral ischemic stroke by activating JAK2/STAT3 axis.

       

      • HTML全文
      • 参考文献(26)
      • 相关文章
      • 施引文献
    • 资源附件(0)

    /

    返回文章
    返回