FK506结合蛋白52对人子宫内膜间质细胞增殖作用的影响

doi:10.6040/j.issn.1671-7554.0.2018.1165

摘要/Abstract

摘要： 目的探讨FK506结合蛋白52(FKBP52)对人子宫内膜间质细胞(HESCs)增殖的影响,为薄型子宫内膜的治疗提供新的依据和靶点。方法分离并培养原代HESCs,分别感染过表达FKBP52的慢病毒和转染靶向沉默FKBP52的小干扰RNA(siRNA),CCK8法检测细胞增殖活性,平板克隆形成实验检测细胞克隆形成能力,流式细胞分析法检测细胞周期的变化,Western blotting法检测FKBP52及细胞周期相关蛋白表达水平。结果过表达FKBP52后,子宫内膜间质细胞的增殖活性增强(P<0.05),细胞克隆形成能力提高(P<0.01),细胞周期进程加快(P<0.01),细胞周期素依赖激酶4(CDK4)、细胞周期蛋白D1(CyclinD1)、细胞周期素依赖激酶2(CDK2)及细胞周期蛋白E1(CyclinE1)的蛋白表达水平均升高(P<0.05);干扰FKBP52后, 子宫内膜间质细胞的增殖能力减弱(P<0.05),细胞克隆形成能力降低(P<0.05),细胞周期进程受阻滞(P<0.05),CDK4、CyclinD1、CDK2、CyclinE1的表达均被抑制(P<0.05)。结论 FKBP52可通过促进HESCs的细胞周期进程来促进HESCs的增殖,有可能作为薄型子宫内膜治疗的靶点。

关键词: FK506 结合蛋白52, 细胞增殖, 细胞周期, 薄型子宫内膜, 子宫内膜间质细胞

Abstract: Objective To explore the effects of FK506 binding protein 52(FKBP52)on proliferation of human endometrial stromal cells(HESCs), and provide the new basis and target for treatment of thin endometrium. Methods Normal HESCs were isolated and cultured. After infecting HESCs with lentiviruses contain GFP-FKBP52 or transfecting HESCs with FKBP52-targeting small interfering RNA(siRNA)to overexpress or knockdown FKBP52 respectively, the cells proliferation and colony-formation were compared with CCK8 assay and plate clone formation assay. Besides, changes in cell cycle were detected by flowcytometry and expression levels of FKBP52 and cell cycle-related proteins were examined by Western blotting. Results After overexpressing FKBP52, the proliferation activity of HESCs was enhanced(P<0.05), and the clone formation ability of cells was improved(P<0.01). The process of cell cycle was accelerated(P<0.01)and the expression levels of cell cycle dependent kinase 4(CDK4), CyclinD1, cell cycle dependent kinase 2(CDK2)and CyclinE1 were increased(P<0.05). Affected by FKBP52 knockdown in transfected cell, the proliferation capacity of endometrial stromal cells was reduced(P<0.05), and the clone formation capacity was weakened(P<0.05). The cell cycle process was blocked(P<0.05)and expression levels of CDK4, CyclinD1,CDK2 and CyclinE1 were suppressed(P<0.05). Conclusion FKBP52 can control the proliferation of HESCs by regulating the cell 山东大学学报 (医学版)57卷2期 -阎慧丽,等.FK506结合蛋白52对人子宫内膜间质细胞增殖作用的影响 \=- cycle and can be considered as a target for the treatment of thin endometrium.

Key words: FK506 binding protein 52, Cell proliferation, Cell cycle, Thin endometrium, Endometrial stromal cell

中图分类号:

R711.7

阎慧丽,魏慕筠,颜磊,赵跃然. FK506结合蛋白52对人子宫内膜间质细胞增殖作用的影响[J]. 山东大学学报 (医学版), 2019, 57(2): 80-87.

YAN Huili, WEI Muyun, YAN Lei, ZHAO Yueran. Effect of FK506 binding protein 52 on proliferation of human endometrial stromal cells[J]. Journal of Shandong University (Health Sciences), 2019, 57(2): 80-87.

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