在正常的垂体细胞中通过抑制性GPCR调节FGF2诱导的增殖
Liliana Del V Sosa1,2, Florencia Picech1,2, Pablo Perez1,2
1Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Centro de Microscopía Electrónica, Córdoba, Argentina.
Frontiers in endocrinology
|August 14, 2023
概括
索马托斯塔丁模拟剂 (SSTa) 通过激活GPCR-Gαi信号,抑制基本纤维细胞生长因子 (FGF2) 诱导的垂体细胞增殖. 这种途径通过MEK-依赖的机制阻止细胞循环的进展,影响细胞可塑性.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 分子信号传输的方法
背景情况:
- 细胞内通信对于前垂体腺的可塑性至关重要.
- 已知基本纤维细胞生长因子 (FGF2) 影响垂体细胞增殖.
研究的目的:
- 调查G蛋白结合受体Gαi (GPCR-Gαi) 信号是否调节正常垂体细胞中的FGF2诱导的增殖.
- 阐明参与FGF2和GPCR-Gαi之间的相互作用的信号通路.
主要方法:
- 使用来自雌性Wistar大鼠的原发前垂体细胞培养物.
- 细胞被单独用FGF2或索马托斯坦类型 (SSTa) 或与GPCR-Gαi (咳毒素) 抑制剂,MEK (U0126) 或PI3K (LY294002) 联合治疗.
主要成果:
- FGF2增加了BrdU的吸收,而SSTa则减少了乳营养菌和体营养菌的吸收.
- SSTa联合化阻止了FGF2诱导的S相进入,而PTX,U0126或LY294002则逆转了这一效应.
- 通过SSTa抑制增殖与下调的c-Jun,减少化ERK和AKT,降低环林D1和增加p27和p21表达有关.
结论:
- 由SSTa激活的GPCR-Gαi有效地阻断了FGF2在正常垂体细胞中的增殖作用.
- 这种封锁通过一个依赖MEK的机制发生,突出其在调节G1到S阶段过渡中的作用.
- 这些发现表明GPCR-Gαi在垂体细胞可塑性中的调节作用.
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