乙肝病毒通过调控miR-21-5p/STAT3通路促进骨髓来源抑制细胞的增殖与活性

Hepatitis B virus promotes the proliferation and activity of myeloid-derived suppressor cells by regulating the miR-21-5p/STAT3 pathway

目的:探究乙肝病毒(HBV)对骨髓来源抑制细胞(MDSCs)的作用及其机制。方法:C57BL/6小鼠分为正常组和乙肝组,乙肝组建立慢性HBV感染模型,检测小鼠miR-21-5p水平;另将C57BL/6小鼠分为对照组、miR-21-5p阴性对照组、miR-21-5p过表达组和miR-21-5p沉默组,除对照组外其余小鼠注射miR-21-5p干预,除miR-21-5p阴性对照组外,所有小鼠建立慢性HBV感染小鼠模型,检测小鼠miR-21-5p水平及MDSCs数量;将miR-21-5p分别转染小鼠MDSCs,暴露于HBV病毒中,检测p-STAT3(Ser727)、Arginase-1、IL-10及p-STAT3蛋白水平;在培养基中加入Stattic(STAT3抑制剂),检测p-STAT3、Arginase-1以及IL-10蛋白水平。结果:乙肝组miR-21-5p表达水平高于正常组;miR-21-5p阴性对照组相较于对照组miR-21-5p表达水平及MDSCs数量升高,miR-21-5p过表达组相较于miR-21-5p沉默组miR-21-5p表达水平及MDSCs数量升高;小鼠MDSCs感染HBV后p-STAT3(Ser727)、Arginase-1、IL-10及p-STAT3蛋白表达升高,miR-21-5p过表达后p-STAT3(Ser727)、Arginase-1、IL-10及p-STAT3蛋白表达升高;加入Stattic后,p-STAT3、Arginase-1以及IL-10蛋白表达无差异。结论:HBV可能通过调控miR-21-5p/STAT3通路,从而促进MDSCs的增殖与活性。

Objective:To investigate the mechanism of hepatitis B virus(HBV)on myeloid-derived suppressor cells(MDSCs).Methods:C57BL/6 mice were allocated into normal and HBV groups.The chronic HBV infection model was established within the HBV group,with subsequent assessment of miR-21-5p levels in mice.Additionally,C57BL/6 mice were distributed across control,miR-21-5p negative control,miR-21-5p overexpression,and miR-21-5p knockdown groups.All mice,except those in the control group,were subjected to miR-21-5p lentiviral intervention,followed by the establishment of a chronic HBV infection mouse model.Levels of miR-21-5p and MDSCs were measured in mice.Mouse MDSCs were transfected with miR-21-5p lentivirus,exposed to HBV,and subsequent levels of p-STAT3(Ser727),Arginase-1,IL-10,and p-STAT3 proteins were assessed.Stattic was introduced into the culture medium to evaluate levels of p-STAT3,Arginase-1,and IL-10 proteins.Results:The HBV group exhibited a higher miR-21-5p expression level compared to the normal group.Compared with the control group,miR-21-5p expression levels and MDSC counts increased in the miR-21-5p negative control group,whereas both increased in the miR-21-5p overexpression group compared with the miR-21-5p knockdown group.Following the HBV infection of mouse MDSCs,there was a marked elevation in the expression of p-STAT3(Ser727),Arginase-1,IL-10,and p-STAT3 proteins.Similarly,miR-21-5p overexpression led to increased expression of p-STAT3(Ser727),Arginase-1,IL-10,and p-STAT3 proteins.Notably,upon Stattic administration,there was no discernible difference in the expression of p-STAT3,Arginase-1,and IL-10 proteins.Conclusion:HBV potentially fosters the proliferation and functional activity of MDSCs through the modulation of the miR-21-5p/STAT3 pathway.