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

doi:10.3870/j.issn.1672-8009.2026.03.003

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (3): 250-257.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

韦雪^1#, 龚浩^1#, 张倩¹, 董书琴¹, 韦静², 卢宇¹

南京医科大学泰州临床医学院,南京医科大学附属泰州人民医院¹内分泌科,²妇产科江苏省泰州市,225300

收稿日期:2025-12-24 发布日期:2026-06-01
通讯作者: 卢宇(E-mail:luyu_666@126.com)
作者简介:#:共同第一作者
基金资助:
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)

Agouti Signaling Protein Promotes Trophoblast Cell Proliferation,Invasion,and Tube Formation Through PPARγ Under High-Glucose Conditions

WEI Xue^1#, GONG Hao^1#, ZHANG Qian¹, DONG Shuqin¹, WEI Jing², LU Yu¹

¹Department of Endocrinology,²Department of Obstetrics and Gynecology,the Affiliated Taizhou People’s Hospital of Nanjing Medical University,Taizhou School of Clinical Medicine,Nanjing Medical University,Taizhou,Jiangsu,225300,China

Received:2025-12-24 Published:2026-06-01
Contact: LU Yu(E-mail:luyu_666@126.com)
About author:#:These authors contributed equally as first author.
Supported by:
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)

摘要/Abstract

摘要： 目的探索刺鼠信号蛋白(agouti signaling protein,ASIP)在不同糖耐量孕妇胎盘中的表达及在高糖环境下对滋养层细胞增殖、侵袭和成管能力的影响。方法纳入妊娠期糖尿病(gestational diabetes mellitus,GDM)孕妇和非GDM孕妇各20例。应用免疫组织化学和免疫荧光染色检测胎盘组织中ASIP的表达和定位。采用高糖培养的人滋养层细胞系HTR-8/SVneo细胞模型,分别给予重组人ASIP蛋白与过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ,PPARγ)的拮抗剂GW9662处理,通过MTT、Transwell及Matrigel实验评估细胞增殖、侵袭与成管能力。采用蛋白质印迹和RT-qPCR分析相关蛋白及mRNA表达。结果 GDM组胎盘重量较非GDM组明显增加(570 g vs 490 g,P=0.019)。RT-qPCR和蛋白质印迹结果表明GDM胎盘中ASIP的mRNA及蛋白表达明显升高,免疫组织化学和免疫荧光染色检测进一步证实在胎盘绒毛滋养层细胞中ASIP蛋白表达明显升高。在高糖环境下,HTR-8/SVneo细胞中ASIP的mRNA及蛋白水平的表达明显增加,重组人ASIP蛋白(50~200 ng/mL)以剂量依赖性的方式促进HTR-8/SVneo细胞增殖,诱导PPARγ、信号转导与转录激活因子1(signal transducer and activator of transcription 1,STAT1)和STAT3的磷酸化。ASIP(200 ng/mL)作用HTR-8/SVneo细胞24 h后,细胞的增殖、侵袭和成管能力均显著增强,加入PPARγ拮抗剂GW9662(20 μmol/L)后上述效应可被部分逆转(P_均<0.01)。结论 GDM/高糖环境下胎盘滋养层细胞中ASIP表达升高,ASIP通过PPARγ依赖性机制促进高糖环境下滋养层细胞的过度增殖、侵袭及成管,从而参与GDM病理性胎盘重塑。

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γ

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-glucose conditions,on trophoblast cell proliferation,invasion,and tube formation. Methods Placental 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 immunohistochemistry 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-activated 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 expression 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 induced 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 formation.The promoting effects of ASIP were partially reversed by co-treatment with the PPARγ antagonist 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.

Key words: agouti signaling protein, trophoblast, placenta, gestational diabetes mellitus, peroxisome proliferator-activated receptor γ

中图分类号:

R714.256

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.

WEI Xue, GONG Hao, ZHANG Qian, DONG Shuqin, WEI Jing, LU Yu. Agouti Signaling Protein Promotes Trophoblast Cell Proliferation,Invasion,and Tube Formation Through PPARγ Under High-Glucose Conditions[J]. Journal of Medical Molecular Biology, 2026, 23(3): 250-257.

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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

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