胎盘滋养层细胞内质网应激诱导的促炎作用参与妊娠期糖尿病的发生

Q4 Medicine

中华围产医学杂志 Pub Date : 2019-10-16 DOI:10.3760/CMA.J.ISSN.1007-9408.2019.10.007

Meng-zhou He, Jing Jia, Jing-yi Zhang, Xuan Zhou

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The expression of glucose-regulated protein-78 (GRP-78), a marker protein for endoplasmic reticulum stress, and C/EBP homologous protein (CHOP) were detected using Western blotting. Five placental tissue samples were collected from normal gravidas for explant culture. Three subgroups were set up according to different culturing methods including culturing with IL-1β (5 ng/ml) for 20 h (IL-1β model group), 30 μmol/L thapsigargin (TG, an endoplasmic reticulum stress agonist) for 2 h after treating with IL-1β (5 ng/ml) for 18 h (IL-1β+TG intervention group) or with no stimulation (blank control group). Western blotting was used to detect the expressions of GRP-78, CHOP and glucose transporter 4 (GLUT4) in placenta explants. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). 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(3) Compared with the blank control group, the expression of GRP-78 and CHOP protein in the IL-1β model group increased significantly (0.87±0.18 vs 0.36±0.07, t=2.67; 1.14±0.09 vs 0.78±0.06, t=3.20; both P<0.05); but the expression of GLUT4 protein significantly decreased (1.00±0.14 vs 2.21±0.49, t=2.40, P<0.05); the expressions of IL-6 and TNF-α mRNA significantly increased (0.89±0.23 vs 0.30±0.06, t=2.31; 0.62±0.16 vs 0.17±0.09, t=2.29; both P<0.05). Compared with the IL-1β model group, the expression of GRP-78 and CHOP protein significantly increased in IL-1β+TG group (2.02±0.32 vs 0.87±0.18, t=3.11; 2.18±0.31 vs 1.14±0.09, t=3.16; both P<0.05); the expression of GLUT4 protein significantly decreased (0.39±0.19 vs 1.00±0.14, t=2.66, P<0.05); the expression of IL-6 and TNF-α mRNA increased significantly (1.67±0.25 vs 0.89±0.23, t=2.26; 1.42±0.27 vs 0.62±0.16, t=2.51; both P<0.05). \n \n \nConclusions \nEndoplasmic reticulum stress may be associated with increased release of pro-inflammatory cytokines in placental tissues of some GDM women and involved in the onset and development of GDM. \n \n \nKey words: \nDiabetes, gestational; Endoplasmic reticulum stress; Placenta; Cytokines; Inflammation","PeriodicalId":52320,"journal":{"name":"中华围产医学杂志","volume":"22 1","pages":"722-728"},"PeriodicalIF":0.0000,"publicationDate":"2019-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pro-inflammatory effect induced by endoplasmic reticulum stress in placental trophoblast cells participates in genesis of gestational diabetes mellitus\",\"authors\":\"Meng-zhou He, Jing Jia, Jing-yi Zhang, Xuan Zhou\",\"doi\":\"10.3760/CMA.J.ISSN.1007-9408.2019.10.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Objective \\nTo explore whether the pro-inflammatory effect of endoplasmic reticulum stress in placental tissues involves in the genesis of gestational diabetes mellitus (GDM). \\n \\n \\nMethods \\nForty gravidas who underwent regular prenatal examinations and delivered at Tongji Hospital were recruited from January to December, 2016. 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引用次数: 0

摘要

目的探讨胎盘组织内质网应激的促炎作用是否参与妊娠期糖尿病的发生。方法选取2016年1 - 12月在同济医院进行常规产前检查的产妇40例。其中，GDM妇女20例(GDM组)，其余20例作为对照，从未患GDM的妇女中选择年龄、胎周与GDM组相匹配的妇女。取两组胎盘组织。透射电镜下观察了滋养细胞内质网的超微结构。Western blotting检测内质网应激标记蛋白葡萄糖调节蛋白-78 (GRP-78)和C/EBP同源蛋白(CHOP)的表达。从正常妊娠中采集5个胎盘组织样本进行外植体培养。按不同的培养方法分为3个亚组:IL-1β (5 ng/ml)培养20 h (IL-1β模型组)，IL-1β (5 ng/ml)治疗18 h (IL-1β+TG干预组)后30 μmol/L thapsigargin (TG，内质网应激激动剂)培养2 h(空白对照组)。Western blotting检测胎盘外植体中GRP-78、CHOP和GLUT4的表达。采用实时荧光定量聚合酶链式反应(RT-PCR)检测白细胞介素-6 (IL-6)和肿瘤坏死因子-α (TNF-α) mRNA表达。统计学分析采用单因素方差分析、LSD和t检验。结果(1)GDM组滋养细胞内质网池池数量增多，池池大小增大。电镜下可见内质网明显扩张，碎片和囊泡大小不一。对照组胎盘组织内质网未见明显肿胀。(2) GDM组GRP-78、CHOP蛋白表达高于对照组(0.90±0.17 vs 0.48±0.08,t=2.24;0.85±0.13 vs 0.46±0.12,t=2.10;P < 0.05)。(3)与空白对照组比较，IL-1β模型组GRP-78、CHOP蛋白表达显著升高(0.87±0.18 vs 0.36±0.07,t=2.67;1.14±0.09 vs 0.78±0.06,t=3.20;均P < 0.05);GLUT4蛋白表达显著降低(1.00±0.14 vs 2.21±0.49,t=2.40, P<0.05);IL-6、TNF-α mRNA表达量显著升高(0.89±0.23 vs 0.30±0.06,t=2.31);0.62±0.16 vs 0.17±0.09,t=2.29;P < 0.05)。与IL-1β模型组比较，IL-1β+TG组GRP-78、CHOP蛋白表达显著升高(2.02±0.32 vs 0.87±0.18,t=3.11;2.18±0.31 vs 1.14±0.09,t=3.16;均P < 0.05);GLUT4蛋白表达量显著降低(0.39±0.19 vs 1.00±0.14,t=2.66, P<0.05);IL-6、TNF-α mRNA表达显著升高(1.67±0.25 vs 0.89±0.23,t=2.26);1.42±0.27 vs 0.62±0.16,t=2.51;P < 0.05)。结论内质网应激可能与部分GDM妇女胎盘组织促炎细胞因子释放增加有关，参与了GDM的发生和发展。关键词:糖尿病;妊娠期;内质网应力;胎盘;细胞因子;炎症

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Pro-inflammatory effect induced by endoplasmic reticulum stress in placental trophoblast cells participates in genesis of gestational diabetes mellitus

Objective To explore whether the pro-inflammatory effect of endoplasmic reticulum stress in placental tissues involves in the genesis of gestational diabetes mellitus (GDM). Methods Forty gravidas who underwent regular prenatal examinations and delivered at Tongji Hospital were recruited from January to December, 2016. Among them, 20 were GDM women (GDM group), and the remaining twenty were served as the control, which were selected from those without GDM and matched for age and gestational weeks to the GDM group. Placental tissues were collected from the two groups. The ultrastructure of endoplasmic reticulum in trophoblast cells was observed under transmission electron microscope. The expression of glucose-regulated protein-78 (GRP-78), a marker protein for endoplasmic reticulum stress, and C/EBP homologous protein (CHOP) were detected using Western blotting. Five placental tissue samples were collected from normal gravidas for explant culture. Three subgroups were set up according to different culturing methods including culturing with IL-1β (5 ng/ml) for 20 h (IL-1β model group), 30 μmol/L thapsigargin (TG, an endoplasmic reticulum stress agonist) for 2 h after treating with IL-1β (5 ng/ml) for 18 h (IL-1β+TG intervention group) or with no stimulation (blank control group). Western blotting was used to detect the expressions of GRP-78, CHOP and glucose transporter 4 (GLUT4) in placenta explants. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Statistical analysis was performed using one-way analysis of variance, LSD and t test. Results (1) In the GDM group, increased number and size of endoplasmic reticulum cisternae were observed in trophoblast cells. Moreover, obviously dilated endoplasmic reticulum and different size of fragments and vesicles were also seen under electron microscope. While the endoplasmic reticulum in the placental tissues of the control group showed no obvious swelling. (2) The expression of GRP-78 and CHOP protein in the GDM group were higher than those in the control group (0.90±0.17 vs 0.48±0.08, t=2.24; 0.85±0.13 vs 0.46±0.12, t=2.10; both P<0.05). (3) Compared with the blank control group, the expression of GRP-78 and CHOP protein in the IL-1β model group increased significantly (0.87±0.18 vs 0.36±0.07, t=2.67; 1.14±0.09 vs 0.78±0.06, t=3.20; both P<0.05); but the expression of GLUT4 protein significantly decreased (1.00±0.14 vs 2.21±0.49, t=2.40, P<0.05); the expressions of IL-6 and TNF-α mRNA significantly increased (0.89±0.23 vs 0.30±0.06, t=2.31; 0.62±0.16 vs 0.17±0.09, t=2.29; both P<0.05). Compared with the IL-1β model group, the expression of GRP-78 and CHOP protein significantly increased in IL-1β+TG group (2.02±0.32 vs 0.87±0.18, t=3.11; 2.18±0.31 vs 1.14±0.09, t=3.16; both P<0.05); the expression of GLUT4 protein significantly decreased (0.39±0.19 vs 1.00±0.14, t=2.66, P<0.05); the expression of IL-6 and TNF-α mRNA increased significantly (1.67±0.25 vs 0.89±0.23, t=2.26; 1.42±0.27 vs 0.62±0.16, t=2.51; both P<0.05). Conclusions Endoplasmic reticulum stress may be associated with increased release of pro-inflammatory cytokines in placental tissues of some GDM women and involved in the onset and development of GDM. Key words: Diabetes, gestational; Endoplasmic reticulum stress; Placenta; Cytokines; Inflammation

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来源期刊

中华围产医学杂志 Medicine-Obstetrics and Gynecology

CiteScore

0.70

自引率

0.00%

发文量

4446

期刊介绍： Chinese Journal of Perinatal Medicine was founded in May 1998. It is one of the journals of the Chinese Medical Association, which is supervised by the China Association for Science and Technology, sponsored by the Chinese Medical Association, and hosted by Peking University First Hospital. Perinatal medicine is a new discipline jointly studied by obstetrics and neonatology. The purpose of this journal is to "prenatal and postnatal care, improve the quality of the newborn population, and ensure the safety and health of mothers and infants". It reflects the new theories, new technologies, and new progress in perinatal medicine in related disciplines such as basic, clinical and preventive medicine, genetics, and sociology. It aims to provide a window and platform for academic exchanges, information transmission, and understanding of the development trends of domestic and foreign perinatal medicine for the majority of perinatal medicine workers in my country.