首页|RGC-32通过调节肝癌中Wnt/β-catenin信号诱导Treg/Th17失衡的研究

RGC-32通过调节肝癌中Wnt/β-catenin信号诱导Treg/Th17失衡的研究

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目的:研究肝癌患者中RGC-32 水平与Treg/Th17 细胞比率相关性,初步探究RGC-32 对Wnt/β-catenin信号通路的调节作用.方法:采用酶联免疫吸附试验(ELISA)检测健康对照和肝癌患者血浆中RGC-32、IL-17、IL-22、TGF-β1、IL-10 表达水平;采用流式细胞术检测健康对照和肝癌患者外周血中Th17 细胞和Treg细胞数;采用siRNA转染敲低单个核细胞(PMBC)中RGC-32 水平,通过蛋白质免疫印迹(Western blot)检测RGC-32 敲低后对Wnt/β-catenin信号通路的影响.结果:与健康对照比较,肝癌患者血浆中RGC-32 水平显著升高(P<0.01),Th17 细胞数升高而Treg细胞数下降,Treg/Th17 细胞比率显著下降(P<0.01).与健康对照比较,肝癌患者血浆中Th17 细胞分泌的促炎细胞因子IL-17 和IL-22 显著升高(P<0.01),而Treg细胞分泌的抗炎细胞因子TGF-β1 和IL-10 显著下降(P<0.01).线性回归分析显示,在健康对照中RGC-32 水平与Treg/Th17 无相关性(P>0.05),在肝癌患者中RGC-32 水平与Treg/Th17 呈负相关(P<0.01).敲低RGC-32 后,检测到促炎细胞因子IL-17 表达下降(P<0.01),抗炎因子TGF-β1 表达升高(P<0.01),Wnt/β-catenin信号的激活被抑制.结论:RGC-32 的上调导致肝癌患者Treg/Th17 细胞的失衡,RGC-32 下调能抑制Wnt/β-catenin信号的激活.
RGC-32 induces the imbalance of Treg/Th17 by regulating Wnt/β-catenin signaling in patients with liver cancer
Objective:To investigate the correlation between the level of RGC-32 and the ratio of Treg/Th17 cells in patients with liver cancer,and to explore the regulatory effect of RGC-32 on Wnt/β-catenin signaling pathway.Methods:The expression levels of RGC-32,IL-17,IL-22,TGF-β1 and IL-10 in plasma of healthy controls and liver cancer patients were detected by ELISA.Flow cytometry was used to detect Th17 cells and Treg cells in peripheral blood of healthy controls and patients with liver cancer.The level of RGC-32 in mononuclear cells(PMBC)was reduced by siRNA transfection,and the effect of RGC-32 knockdown on Wnt/β-catenin signaling pathway was detected by Western blot.Results:Compared with healthy controls,the level of RGC-32 in liver cancer patients was significantly increased(P<0.01),the number of Th17 cells was increased while the number of Treg cells was decreased,and the ratio of Treg/Th17 cells was significantly decreased(P<0.01).Compared with healthy controls,the proinflammatory cytokines IL-17 and IL-22 secreted by Th17 cells were significantly increased in liver cancer patients(P<0.01),while the anti-inflammatory cytokines TGF-β1 and IL-10 secreted by Treg cells were significantly decreased(P<0.01).By linear regression analysis,the results showed that there was no correlation between the level of RGC-32 and Treg/Th17 in healthy controls(P>0.05),but a negative correlation between the level of RGC-32 and Treg/Th17 in patients with liver cancer(P<0.01).After knockdown of RGC-32,the expression of pro-inflammatory cytokine IL-17 was decreased(P<0.01),the expression of anti-inflammatory cytokine TGF-β1 was increased(P<0.01),and the activation of Wnt/β-catenin signal was inhibited.Conclusion:The up-regulation of RGC-32 leads to the imbalance of Treg/Th17 cells in patients with liver cancer,and the down-regulation of RGC-32 can inhibit the activation of Wnt/β-catenin signal.

response gene to complement 32cellular immunityregulatory T cellsliver cancer

李玲玲、张云芳、于风格、赵鹏

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青岛市胶州中心医院检验科(山东 青岛,266399)

青岛市即墨区急救中心

青岛市中心医院中心实验室

肝癌 补体反应基因32 细胞免疫 调节性T细胞

2021年度青岛市医药卫生科研计划项目

2021-WJZD120

2024

中西医结合肝病杂志
中国中西医结合学会,湖北中医学院

中西医结合肝病杂志

CSTPCD
影响因子:0.908
ISSN:1005-0264
年,卷(期):2024.34(9)