ARID1A recruits GATA2 to regulate the senescence of trophoblast cells under high-glucose condition

IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Placenta Pub Date : 2024-10-21 DOI:10.1016/j.placenta.2024.10.012
Yanyi Huang , Xiting Yang , Yuexiao Wang, Yaru Nai, Lulu Ji, Hengxuan Zhu, Rujie Lai, Qiong tao Wang, Hanyang Hu, Lin Wang
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Abstract

Introduction

Gestational diabetes mellitus (GDM) is a common complication during pregnancy. The hyperglycemic stimulation of gestational diabetes inhibits the invasion of the placental trophoblast cells. Some studies have indicated that the senescence of trophoblast cells weakens their invasive capacity, while the mechanism of trophoblast cells senescence in GDM remain elusive.

Methods

We performed western blotting and Immunohistochemical staining to investigate AT-Rich Interaction Domain 1A (ARID1A) expression in GDM placental tissues. 5 mM and 30 mM glucose treated HTR-8/SVneo cells to simulate normal glucose (NG) stress and high glucose (HG) stress. Cell proliferation capacity was investigated by CCK8 assay and cell cycle assay. SA-β-gal was used to detect cellular senescence. Chip-seq characterized the binding site of ARID1A to CDKN1A. In conjunction with bioinformatics analysis, co-immunoprecipitation assays, Chip-qPCR and luciferase reporter assays were performed to prove ARID1A recruits GATA2 to CDKN1A.

Results

We found that ARID1A has a higher expression levels in GDM placental tissues compared to the control. ARID1A overexpression suppressed cell proliferation, induced cell cycle arrest and promoted cell senescence. Conversely the inhibition of ARID1A significantly rescues HG induced senescence of trophoblast cells. To further characterize the mechanism by which ARID1A regulate the transcription of CDKN1A, co-immunoprecipitation assays, Chip-qPCR and luciferase reporter assay indicate that ARID1A recruits GATA2 to regulate the transcriptional activity of CDKN1A.

Discussion

Our study uncovers a ARID1A mediated regulatory mechanism in GDM trophoblast cell senescence and suggests that targeting the placental ARID1A might provide new diagnostic and therapeutic strategies for GDM.
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ARID1A 招募 GATA2 以调控高葡萄糖条件下滋养层细胞的衰老
导言妊娠糖尿病(GDM)是孕期常见的并发症。妊娠糖尿病的高血糖刺激会抑制胎盘滋养层细胞的侵入。一些研究表明,滋养层细胞的衰老会削弱其侵袭能力,而 GDM 中滋养层细胞衰老的机制尚不明确。方法 我们采用免疫印迹和免疫组化染色法研究 AT-Rich Interaction Domain 1A (ARID1A) 在 GDM 胎盘组织中的表达。用 5 mM 和 30 mM 葡萄糖处理 HTR-8/SVneo 细胞,模拟正常葡萄糖(NG)应激和高葡萄糖(HG)应激。细胞增殖能力通过 CCK8 检测和细胞周期检测进行研究。SA-β-gal 用于检测细胞衰老。芯片-序列分析鉴定了ARID1A与CDKN1A的结合位点。结果我们发现,与对照组相比,ARID1A在GDM胎盘组织中的表达水平更高。过表达 ARID1A 可抑制细胞增殖、诱导细胞周期停滞并促进细胞衰老。相反,抑制 ARID1A 能明显缓解 HG 诱导的滋养层细胞衰老。为了进一步阐明ARID1A调控CDKN1A转录的机制,共免共沉淀实验、芯片-qPCR和荧光素酶报告实验表明,ARID1A招募GATA2来调控CDKN1A的转录活性。
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来源期刊
Placenta
Placenta 医学-发育生物学
CiteScore
6.30
自引率
10.50%
发文量
391
审稿时长
78 days
期刊介绍: Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.
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