通过ATF2介导的USP4的转录激活稳定了KMT2A蛋白,并促进了热囊细胞功能障碍
Jialin Liu1, Ke Pan2, Chunli Yang1
1Department of Clinical Laboratory, Mianyang Maternity and Child Healthcare Hospital & Mianyang Children's Hospital, Mianyang, Sichuan, 621000, China.
Reproductive sciences (Thousand Oaks, Calif.)
|August 14, 2025
概括
孕前包括胎盘缺氧和炎症. 激活转录因子2 (ATF2) 激活USP4,这稳定了KMT2A,影响热囊细胞损伤和孕前的铁.
科学领域:
- 产科和妇科 产科和妇科
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 孕前 (PE) 是一种妊娠并发症,由胎盘缺氧,炎症和受损的热囊细胞入侵驱动.
- 了解PE的分子机制对于开发有效的治疗策略至关重要.
研究的目的:
- 调查激活转录因子2 (ATF2),乌比奎丁特异性酶4 (USP4) 和酸甲基转移酶2A (KMT2A) 在孕前病原发生中的作用.
- 为了阐明涉及ATF2,USP4和KMT2A的分子途径,在缺氧/再氧化处理的热囊细胞中.
主要方法:
- 使用HTR-8/SVneo热原体细胞建立了体外低氧/低氧化 (H/R) 模型.
- 通过使用MTT,EdU,流细胞计,跨井测定和商业套件评估细胞增殖,细胞亡,入侵和铁亡.
- 利用RT-qPCR,西部抹杀,共同免疫沉降 (Co-IP),无化试验,双化酶记者试验和染色体免疫沉降 (ChIP) 试验来确定分子相互作用和调节途径.
主要成果:
- KMT2A的敲除加剧了H/R诱导的热细胞增殖和入侵,同时抑制了亡和铁亡.
- USP4使KMT2A脱和稳定,其过度表达逆转了USP4沉默对H/R诱导的细胞损伤和铁亡的影响.
- ATF2通过转录激活了USP4表达,USP4的上调调节拯救了ATF2枯竭诱导的HTR-8/SVneo细胞损伤和铁亡.
结论:
- 在H/R条件下,ATF2-USP4-KMT2A通路在调节热囊细胞行为和铁亡中发挥着重要作用,有助于孕前的发展.
- 这项研究为治疗干预提供了一种新的理论基础,该干预措施针对产前的ATF2-USP4-KMT2A轴.
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