实用医学杂志 ›› 2021, Vol. 37 ›› Issue (15): 1928-1933.doi: 10.3969/j.issn.1006⁃5725.2021.15.004

• 基础研究 • 上一篇    下一篇

全反式维甲酸通过调控sFlt-1表达对滋养层细胞侵袭及促血管形成能力的影响

阳双健1, 钟黎黎1, 盛莹1 ,郭江虹1, 何宜静2    

  1. 1 南华大学衡阳医学院,附属第一医院产科(湖南衡阳 421001);2 南华大学衡阳医学院,附属第二医院妇产科 (湖南衡阳 421001)

  • 出版日期:2021-08-10 发布日期:2021-08-10
  • 通讯作者: 钟黎黎 E⁃mail:lili841114@126.com
  • 基金资助:
    湖南省卫生健康委 2019年度科研计划科研项目(编 号:B2019116)

Effects of ATRA on trophoblast cell invasion and angiogenesis by regulating sFlt⁃1 expression 

YANG Sh⁃ uangjian*,ZHONG Lili,SHENG Ying,GUO Jianghong,HE Yijing.    

  1. The First Affiliated Hospital,Department of Obstetrics,Hengyang Medical School,University of South China,Hengyang 421001,China 

  • Online:2021-08-10 Published:2021-08-10
  • Contact: ZHONG Lili E⁃mail:lili841114@126.com ​

摘要:

目的 探讨全反式维甲酸(ATRA)对可溶性血管内皮生长因子受体 1(sFlt⁃1)的调控作用及其对人胎盘滋养层细胞侵袭及促血管形成能力的影响。方法 采用 0.15 μmol/L ATRA 处理 HTR⁃8/SVneo 细胞 12、24、48、72 h,RT⁃PCR ELISA 分别检测细胞中 sFlt⁃1 mRNA 以及上清液中 sFlt⁃1 蛋白水平。采用 携带 sFlt⁃1 过表达载体慢病毒感染 HTR⁃8/SVneo 细胞,并采用 0.15 μmol/L ATRA 处理 24 h,采用 ELISA 检测细胞上清液中 sFlt⁃1、胎盘生长因子(PIGF)和血管内皮生长因子(VEGF)的蛋白含量;Transwell 实验检测 细胞的侵袭和迁移能力;小管形成实验检测细胞体外促血管形成能力;Western blot 检测细胞中基质金属蛋白酶⁃2(MMP⁃2)和MMP⁃9蛋白表达水平。结果 ATRA可呈时间依赖性的抑制HTR⁃8/SVneo细胞中sFlt⁃ 1 mRNA 表达及其蛋白的分泌;ATRA 干预后,HTR⁃8/SVneo 细胞上清液中 sFlt⁃1 蛋白水平降低(P < 0.05), PIGF VEGF 蛋白水平升高(P < 0.05),而细胞侵袭和迁移能力、血管成管数目以及 MMP⁃9 MMP⁃2 蛋白表达水平均增加(P < 0.05)。然而,sFlt⁃1 过表达可抑制 ATRA HTR⁃8/SVneo 细胞的干预效果。结论 ATRA 可通过抑制sFlt⁃1表达增强滋养层细胞侵袭及促血管形成能力。

关键词: 全反式维甲酸,  , sFlt?1,  , HTR?8/SVneo , 细胞,  , 侵袭

Abstract:

Objective To investigate the regulatory effect of all ⁃trans retinoic acid(ATRA)on soluble vascular endothelial growth factor receptor 1(sFlt⁃1)and its effect on the invasion and angiogenesis of human pla⁃ cental trophoblast cells. Methods HTR⁃8/SVneo cells were treated with 0.15 μM ATRA for 12,24,48 and 72 h, then the expression levels of sFlt⁃1 mRNA and protein were detected by RT⁃PCR and ELISA. HTR⁃8/SVneo cells were infected with sFlt⁃1 overexpresses lentivirus,and treated with 0.15 μmol/L ATRA for 24 h. The protein con⁃ tents of sFlt⁃1,PIGF and VEGF in the cell culture supernatant were detected by ELISA. The abilities of invasion and migration were detected by transwell assay. The pro⁃angiogenesis ability of cells in vitro was tested by tubule formation assay. The protein expression levels of MMP ⁃ 2 and MMP ⁃ 9 were detected by Western blot. Results ATRA inhibited the mRNA expression and protein secretion of sflt ⁃ 1 in HTR ⁃8/SVneo cells in a time ⁃dependent manner;After ATRA treatment,the content of sFlt⁃1 protein in the cell supernatant of HTR⁃8/SVneo cells was de⁃ creased(< 0.05),and the protein contents of PIGF and VEGF were increased(< 0.05),the abilities of inva⁃ sion and migration,the number of vascularization tubes and the protein expression levels of MMP ⁃ 9 and MMP ⁃2 were increased(< 0.05). However,overexpression of sFLT⁃1 inhibited the intervention effect of ATRA on HTR⁃ 8/SVneo cells. Conclusion ATRA enhances trophoblast cell invasion and angiogenesis by inhibiting sflt⁃1 expres⁃ sion.

Key words: ATRA,  , sFlt?1,  , HTR?8/SVneo cells,  , invasion