c-Jun调节分娩后β细胞亡和芽素信号的下游生存
Jin-Yong Chung1, Nelmari Ruiz-Otero1, Ronadip R Banerjee1
1Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, USA.
Molecular and cellular endocrinology
|May 11, 2025
概括
怀孕期间母亲的β细胞质量变化. 这项研究揭示了c-Jun,一种转录因子,通过响应益生素信号,对贝塔细胞产后生存至关重要,其失调与妊娠糖尿病有关.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 生殖生物学 生殖生物学
背景情况:
- 孕妇的胰腺β细胞质量在怀孕和产后经历了显著的变化.
- 贝塔细胞质量的产后回归尚未得到充分理解.
- 识别β细胞亡和生存的调节者对于理解生殖内分泌学至关重要.
研究的目的:
- 研究转录因子c-Jun在孕期和产后调节β细胞质量的作用.
- 阐明涉及到c-Jun调节中的信号通路.
- 检查人类小岛的c-Jun表达及其与妊娠糖尿病的潜在联系.
主要方法:
- 使用了一种缺乏β细胞中益乳素受体 (PRLR) 的小鼠模型.
- 用重组益生菌激发的人类和小鼠小岛.
- 使用siRNA和lentiviral-shRNA以及药物抑制剂进行了c-Jun的淘汰.
- 使用TUNEL染色评估β细胞亡.
- 分析了来自孕妇捐赠者和妊娠期糖尿病 (GDM) 患者的小岛的c-Jun表达.
主要成果:
- 贝塔细胞中的c-Jun表达仅限于妊娠晚期和产后早期,并且依赖于PRLR信号传递.
- 益生菌治疗通过MAPK/ERK信号传递诱导c-Jun表达,在小鼠和人类群岛中.
- c-Jun表达与β细胞亡相反相关.
- 抑制c-Jun通过降低Bcl-xL和Survivin的调节,取消了益生素介导的β细胞存活率.
- 来自孕妇捐赠者的人体小岛显示了c-Jun的增加,而在GDM病例中没有这种情况.
结论:
- 在产后期间,c-Jun作为益生菌对β细胞的促生存效应的关键调解者.
- PRLR/MAPK/c-Jun通路对于维持贝塔细胞功能和怀孕期间的存活至关重要.
- 贝塔细胞中c-Jun的失调与妊娠糖尿病有关,这突显了其临床相关性.
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