高浓度葡萄糖通过Bmi1促进小儿肾母细胞瘤免疫逃逸的机制研究-东南大学学报医学版

高浓度葡萄糖通过Bmi1促进小儿肾母细胞瘤免疫逃逸的机制研究

单位：1. 十堰市妇幼保健院, 湖北十堰 442000;
2. 湖北医药学院附属东风医院, 湖北十堰 442000;
3. 十堰市郧阳区妇幼保健院, 湖北十堰 442000

关键词：高浓度葡萄糖小儿肾母细胞瘤 MHCⅠ类多肽相关序列A MHCⅠ类多肽相关序列B 自然杀伤细胞

分类号：R737.11

出版年·卷·期（页码）：2021·40·第四期（487-493）

摘要：

目的：探讨B细胞特异性MLV整合位点-1（Bmi1）在高浓度葡萄糖介导的小儿肾母细胞瘤逃逸自然杀伤细胞（NK细胞）免疫杀伤中的作用及其机制。方法：免疫组化检测小儿肾母细胞瘤组织和肾母细胞瘤细胞G401中Bmi1的表达；实时荧光定量聚合酶链反应、蛋白质印迹法和流式细胞术检测不同浓度葡萄糖处理的G401细胞中Bmi1、MHCⅠ类多肽相关序列A （MICA）、MICB的mRNA及蛋白表达水平；乳酸脱氢酶释放法检测NK细胞对不同浓度葡萄糖处理的G401细胞的杀伤敏感性。结果：Bmi1在小儿肾母细胞瘤组织和G401细胞中高表达；高浓度葡萄糖处理G401细胞可促进Bmi1表达，抑制MICA和MICB表达，降低NK细胞对G401细胞的杀伤敏感性；沉默Bmi1促进高浓度葡萄糖处理的G401细胞的MICA和MICB表达，增强NK细胞对G401细胞的杀伤敏感性。结论：高浓度葡萄糖通过促进Bmi1表达，抑制MICA和MICB表达，降低NK细胞对G401细胞的杀伤敏感性。

Objective: To investigate the effect of B cell-specific MLV integration site-1(Bmi1) on high concentration glucose-mediated escape of pediatric nephroblastoma cells from immune killing by natural killer(NK) cells. Methods: Immunohistochemistry was used to detect the expression of Bmi1 in pediatric nephroblastoma tissue and nephroblastoma cell G401. qRT-PCR, Western blot and flow cytometry were employed to respectively detect the mRNA and protein levels of Bmi1, MHC classⅠ polypeptide-related sequence A(MICA) and MICB in G401 cells treated with different concentrations of glucose. LDH releasing assay was used to detect the cytotoxicity of NK cells against G401 cells treated with different concentrations glucose. Results: The expression of Bmi1 was up-regulated in pediatric nephroblastoma tissue and G401 cells. The G401 cells treated with high concentrations glucose promoted the Bmi1 expression, inhibited the expression of MICA and MICB, and reduced the cytotoxicity of NK cells against G401 cells. The silencing Bmi1 could promote the expression of MICA and MICB in G401 cells treated with high concentration glucose, and enhance the cytotoxicity of NK cells. Conclusion: High concentration of glucose inhibits the expression of MICA and MICB, and reduces the cytotoxicity of NK cells against G401 cells via increasing Bmi1 expression.

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