医学分子生物学杂志2026，Vol.23Issue(3)：250-257,8.DOI:10.3870/j.issn.1672-8009.2026.03.003
刺鼠信号蛋白通过PPARγ途径促进高糖环境下滋养层细胞的增殖、侵袭和成管能力
Agouti Signaling Protein Promotes Trophoblast Cell Proliferation,Invasion,and Tube Formation Through PPARγ Under High-Glucose Conditions
摘要
Abstract
Objective To investigate the expression of agouti signaling protein(ASIP)in the placenta of pregnant women with different glucose tolerance,as well as its effect,under high-glu-cose conditions,on trophoblast cell proliferation,invasion,and tube formation.Methods Placen-tal tissues were collected from pregnant women with gestational diabetes mellitus(GDM,n=20)and without GDM(non-GDM,n=20).ASIP expression and localization were detected by immuno-histochemistry and immunofluorescence.The human trophoblast cell line HTR-8/SVneo was cultured under high-glucose conditions and treated with recombinant ASIP or the peroxisome proliferator-acti-vated receptor γ(PPARγ)antagonist GW9662.Cell proliferation,invasion,and tube formation were assessed using MTT,Transwell,and Matrigel assays,respectively.Western blotting assay and RT-qPCR were performed to analyze protein and mRNA expression.Results Placental weight was significantly higher in the GDM group than in the non-GDM group(570 g vs 490 g,P=0.019).ASIP mRNA and protein levels were significantly upregulated in GDM placental villous trophoblasts,and immunohistochemistry and immunofluorescence further confirmed significantly increased ASIP protein expression in the placental villous trophoblasts.Under high-glucose conditions,the expres-sion levels of ASIP mRNA and protein in HTR-8/SVneo cells were significantly increased.Subsequently,recombinant ASIP(50-200 ng/mL)promoted cell proliferation and in-duced the phosphorylation of PPARγ,signal transducer and activator of transcription 1(STAT1),and STAT3 in a dose-dependent manner.Furthermore,treatment of HTR-8/SVneo cells with ASIP(200 ng/mL)for 24 h significantly enhanced trophoblast proliferation,invasion,and tube forma-tion.The promoting effects of ASIP were partially reversed by co-treatment with the PPARγ antago-nist GW9662(20 μmol/L).Conclusion ASIP expression is elevated in trophoblast cells under both GDM and high-glucose conditions.ASIP promotes excessive proliferation,invasion,and tube formation of trophoblast cells via a PPARγ-dependent mechanism under high-glucose conditions,thereby contributing to the placental remodeling of GDM.关键词
刺鼠信号蛋白/滋养层细胞/胎盘/妊娠期糖尿病/过氧化物酶体增殖物激活受体γKey words
agouti signaling protein/trophoblast/placenta/gestational diabetes mellitus/peroxisome proliferator-activated receptor γ分类
医药卫生引用本文复制引用
韦雪,龚浩,张倩,董书琴,韦静,卢宇..刺鼠信号蛋白通过PPARγ途径促进高糖环境下滋养层细胞的增殖、侵袭和成管能力[J].医学分子生物学杂志,2026,23(3):250-257,8.基金项目
江苏省"六大人才高峰"项目(No.WSN-336),江苏省卫生健康委科研项目(No.LGY2020067),南京医科大学泰州临床医学院科研项目(No.TZKY20220110) This work was supported by grants from the Six Talent Peaks Project in Jiangsu Province(No.WSN-336),Scientific Research Project of Health Commission in Jiangsu Province(No.LGY2020067),Scientific Research Project of Taizhou School of Clinical Medicine of Nanjing Medical University(No.TZKY20220110). （No.WSN-336）
