膜蛋白酶前列腺素通过调节表皮生长因子受体通路来促进胰岛素分泌
Toshihisa Ishii1, Yoshikazu Miyasato2, Masashi Ichijo3
1Division of Nephrology, University of Yamanashi, Yamanashi, 409-3898, Japan.
Scientific reports
|June 5, 2023
概括
前列腺素 (PRSS8) 通过EGF-EGFR通路调节胰腺β细胞的胰岛素分泌. 这种血清蛋白酶对于葡萄糖刺激的胰岛素释放和β细胞功能至关重要.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 前列腺素 (PRSS8) 是一种涉及调节各种细胞过程的血清蛋白酶.
- 皮表皮生长因子受体 (EGFR) 信号影响胰岛素分泌和胰腺β细胞增殖.
- 在胰腺β细胞中PRSS8和EGFR之间的相互作用仍然不完全理解.
研究的目的:
- 研究prostasin (PRSS8) 在调节胰岛素分泌和胰腺β细胞功能的作用.
- 阐明 PRSS8 中介作用对葡萄糖刺激胰岛素分泌 (GSIS) 的分子机制.
- 为了确定EGF-EGFR信号通路在PRSS8的功能中的参与.
主要方法:
- 产生胰腺β细胞特异性PRSS8淘汰 (βKO) 和PRSS8过度表达 (βTG) 的雄性小鼠.
- 在生成的小鼠模型中评估葡萄糖耐受性和葡萄糖刺激的胰岛素分泌.
- 使用MIN6细胞进行的体外研究涉及PRSS8沉默或过度表达,并使用EGFR抑制剂 (Erlotinib) 治疗.
- 测量胰岛素分泌,EGFR信号激活 (-EGFR) 和内源PRSS8水平.
主要成果:
- βKO小鼠表现出葡萄糖不耐受性和减少GSIS,而βTG小鼠显示出增强的葡萄糖反应.
- 在MIN6细胞中抑制PRSS8损害了GSIS和EGFR信号传递.
- 在MIN6细胞中,PRSS8的过度表达增加了基底和葡萄糖刺激的胰岛素分泌,增加了-EGFR水平.
- 通过抑制降解,暴露于葡萄糖增加了MIN6细胞中的内源PRSS8水平.
结论:
- 前列腺素 (PRSS8) 在依赖葡萄糖的胰岛素分泌调节中起着至关重要的作用.
- EGF-EGFR信号通路是PRSS8在胰腺β细胞中的功能的关键调解者.
- PRSS8对于维持正常的葡萄糖平衡和胰岛素分泌功能至关重要.
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