miR-34b调节CD40/CD40L信号通路参与过敏性紫癜肾炎患者免疫调节的作用研究

The role of miR-34b in regulating CD40/CD40L signaling pathway in immune regulation of patients with Henoch-Schonlein purpura nephritis

目的 探究miR-34b调节CD40/CD40L信号通路参与过敏性紫癜性肾炎(HSPN)患者免疫调节的作用。方法 收集2019年6月~2021年6月HSPN患者84例、HSP患者84例和健康体检者50例。检测CD4^(+)T细胞中miR-34b、CD40L mRNA和蛋白的水平。Pearson检验分析miR-34b和CD40L的相关性。双荧光素酶报告验证miR-34b和CD40L的靶向关系,并分析过表达miR-34b对CD40L的表达的影响。结果HSP组的CD4^(+)T细胞中的miR-34b水平显著低于健康组,CD40L mRNA和蛋白水平显著高于健康组(P<0.05)。HSPN组的miR-34b水平显著低于HSP组,CD40L mRNA和蛋白水平显著高于HSP组(P<0.05)。miR-34b与CD40L mRNA和蛋白分别呈现显著的负相关(P<0.05)。双荧光素酶报告结果显示miR-34b与CD40L靶向结合,过表达miR-34b显著抑制细胞中CD40L mRNA和蛋白水平(P<0.05)。结论 miR-34b可通过靶向抑制CD40L阻断CD40/CD40L信号通路参与HSPN。

Objective To investigate the role of microRNA-34b(miR-34b)in regulating CD40/CD40L signaling pathway in immune regulation of patients with Henoch-Schonlein purpura nephritis(HSPN).Methods 84 patients with HSPN,84 patients with Henoch-Schonlein purpura(HSP)and 50 healthy subjects were collected from June 2019 to June 2021.The levels of miR-34b,CD40L mRNA and protein in CD4^(+)T cells were detected.The correlation between miR-34b and CD40L was analyzed by Pearson test.The targeting relationship between miR-34b and CD40L was verified by dual luciferase reporter assays,and the effect of miR-34b overexpression on CD40L expression was analyzed.Results Thelevel ofmiR-34b in CD4^(+)T cells of HSP group was significantly lower than that of healthy group,and the levels of CD40L mRNA and protein were significantly higher than that of healthy group(P<0.05).The level of miR-34b in HSPN group was significantly lower than that in HSP group,and the levels of CD4OL mRNA and protein were significantly higher than thosein HSP group(P<0.05).The expression of miR-34b was significantly negatively correlated with CD40L,mRNA and protein(P<0.05),respectively.The dual luciferase report assay showed that miR-34b targeted binding to CD40L.Overexpression of miR-34b significantly inhibited levels of CD40L mRNA and protein in cells(P<0.05).Conclusion miR-34b is involved in HSPN by targeting inhibition of CD40L to block the CD40/CD40L signaling pathway.