中国血液净化

中国血液净化 ›› 2024, Vol. 23 ›› Issue (12): 920-925.doi: 10.3969/j.issn.1671-4091.2024.12.008

• 基础研究 • 上一篇    下一篇

SOCS1基因在高糖诱导的小鼠腹膜间皮细胞上皮间质转化中的作用及机制研究

韩小丽   王加伟   卫志锋   王琳琳   郭宝珠   曹艳春   金玉杰   刘圣君   

  1. 075000 张家口，1河北北方学院附属第一医院肾内科
    075131 张家口，2河北省张家口沙岭子医院精神三科
  • 收稿日期:2024-03-27 修回日期:2024-09-12 出版日期:2024-12-12 发布日期:2024-12-12
  • 通讯作者: 刘圣君 E-mail:15530396533@163.com
  • 基金资助:
    2023年度河北省医学科学研究课题(20231412)

The role and mechanism of SOCS1 gene in high glucose-induced epithelial-mesenchymal transformation of peritoneal mesothelial cells in mice

HAN Xiao-li, WANG Jia-wei, WEI Zhi-feng, WANG Lin-lin, GUO Bao-zhu, CAO Yan-chun, JIN Yu-jie, LIU Sheng-jun   

  1. Department of Nephrology, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China; 2Department of Psychiatry, Shalingzi Hospital of Zhangjiakou, Zhangjiakou 075131, China
  • Received:2024-03-27 Revised:2024-09-12 Online:2024-12-12 Published:2024-12-12
  • Contact: 075000 张家口，1河北北方学院附属第一医院肾内科 E-mail:15530396533@163.com

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摘要： 目的  研究细胞因子信号抑制物1(suppressor of cytokine signaling 1，SOCS1)基因在高糖诱导的小鼠腹膜间皮细胞上皮间质转化(epithelial mesenchymal transformation，EMT)中的作用及机制。 方法  培养小鼠腹膜间皮细胞并分组，对照组用普通培养基处理，1.5%组、2.5%组、4.25%组分别加入相应浓度的D-葡萄糖；2.5%+阴性对照(negative control，NC)质粒组2.5%+SOCS1质粒组在含有2.5% D-葡萄糖的培养基中分别转染NC质粒和SOCS1质粒。处理24小时后检测细胞增殖，迁移和侵袭数目，SOCS1、E-钙粘蛋白(cadherin)、N-钙粘蛋白(N-cadherin)、α-平滑肌肌动蛋白(α-smooth muscle actin，α-SMA)的mRNA表达水平，Janus激酶(Janus kinase，JAK)1/磷酸化信号转导和转录激活因子(signal transduction and activator of transcription，STAT)1、JAK2/STAT3通路。 结果  4.25%组小鼠腹膜间皮细胞的增殖水平低于对照组(t=5.051、P=0.002)；1.5%组、2.5%组、4.25%组小鼠腹膜间皮细胞中E-cadherin、SOCS1的mRNA表达水平低于对照组(t=2.774、7.310、9.7813，P=0.032、＜0.001；   t=2.544、6.996、10.733，P=0.044、＜0.001)，N-cadherin(t=2.825、5.121、7.207，P=0.030、＜0.001)、 α-SMA(t=2.527、4.807、6.950，P=0.045、0.003、＜0.001)的表达水平高于对照组；2.5%+SOCS1质粒组小鼠腹膜间皮细胞中JAK1/STAT1和JAK2/STAT3信号通路受抑制，SOCS1的mRNA表达水平和蛋白表达水平、E-cadherin的mRNA表达水平高于2.5%组(t=9.435、9.761、7.690，均P＜0.001)、2.5%+NC质粒组     (t=9.737、9.138、7.132，均P＜0.001)，细胞迁移和侵袭数目、N-cadherin、α-SMA的mRNA表达水平水平低于2.5%组、2.5%+NC质粒组(t=7.350、8.456，P＜0.001；t=8.562、7.697，P＜0.001；t=4.574、4.865，  P=0.004、0.003；t=3.467、3.036，P=0.013、0.023)。 结论  过表达SOCS1基因抑制高糖诱导小鼠腹膜间皮细胞EMT，这一作用与抑制JAK1/STAT1和JAK2/STAT3信号通路相关。

关键词: 腹膜纤维化, 腹膜间皮细胞, 上皮间质转化, 细胞因子信号抑制物1

Abstract: Objective  To investigate the role and mechanism of the suppressor of cytokine signaling 1 (SOCS1) gene in high glucose-induced epithelial-mesenchymal transformation (EMT) of peritoneal mesothelial cells in mice.  Methods  Mouse peritoneal mesothelial cells were cultured and divided into 6 groups: the control group was treated with routine medium; cells cultured in the medium containing 1.5% (83 mmol/L), 2.5% (139 mmol/L) and 4.25% (236 mmol/L) D-glucose formed the 1.5% group, 2.5% group and 4.25% group; cells transfected with negative control plasmid and cultured in the medium containing 2.5% glucose formed the 2.5%+NC plasmid group; cells transfected with SOCS1 plasmid and cultured in the medium containing 2.5% glucose formed the 2.5%+SOCS1 plasmid group. After the treatment for 24h, proliferation, migration and invasion number of the cells, mRNA expression levels of SOCS1, E-cadherin, N-cadherin and α-SMA, and JAK1/STAT1 and JAK2/STAT3 signaling pathways were detected.  Results  In 4.25% group, the proliferation level of peritoneal mesothelial cells was lower than that in control group (t=5.051, P=0.002). In 1.5%, 2.5% and 4.25% groups, the mRNA expression levels of E-cadherin and SOCS1 in peritoneal mesothelial cells were lower than those in control group (E-cadherin mRNA: t=2.774, 7.310 and 9.7813; P=0.032, ＜0.001 and ＜0.001. SOCS1 mRNA: t=2.544, 6.996 and 10.733; P=0.044, ＜0.001 and ＜0.001), while mRNA expression levels of N-cadherin and α-SMA in peritoneal mesothelial cells were higher than those in control group (N-cadherin mRNA: t=2.825, 5.121 and 7.207; P=0.030, ＜0.001 and ＜0.001. α-SMA mRNA: t=2.527, 4.807 and 6.950; P=0.045, 0.003 and ＜0.001). In 2.5%+SOCS1 plasmid group, JAK1/STAT1 and JAK2/STAT3 signaling pathways in peritoneal mesothelium cells were inhibited, the mRNA and protein expression levels of SOCS1 and the mRNA expression level of E-cadherin were higher than those in 2.5% group and 2.5%+NC plasmid group (SOCS1 mRNA: t=9.435 and 9.737, P＜0.001; SOCS1 protein: t=9.761 and 9.138, P＜0.001; E-cadherin mRNA: t=7.690 and 7.132, P＜0.001), and the number of cell migration and invasion and the mRNA expression levels of N-cadherin and α-SMA were lower than those in 2.5% group and 2.5%+NC plasmid group (t=7.350 and 8.456, P＜0.001; t=8.562 and 7.697, P＜0.001; t=4.574 and 4.865, P=0.004 and 0.003; t=3.467 and 3.036, P=0.013, 0.023).  Conclusion Overexpression of SOCS1 gene inhibits high glucose-induced EMT of peritoneal mesothelial cells in mice, which is related to the inhibition of JAK1/STAT1 and JAK2/STAT3 signaling pathways.

Key words: Peritoneal fibrosis, Peritoneal mesothelial cell, Epithelial-mesenchymal transformation, Suppressor of cytokine signaling 1

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