普拉斯塔格兰丁E2通过EP4信号传递抑制了动脉管道的弹性生成
Utako Yokoyama1, Susumu Minamisawa, Aki Shioda
1Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan (U.Y., S.M., A.S., R.I., M.-H.J., Y.I.); the Department of Life Science and Medical Bioscience, Waseda University Graduate School of Advanced Science and Engineering, Tokyo, Japan (S.M., R.I.); the Department of Cell Physiology, Jikei University School of Medicine, Tokyo, Japan (S.M.); the Department of Surgery, Yokohama City University, Yokohama, Japan (M.M.); the Department of Cardiovascular Surgery, Kanagawa Children's Medical Center, Yokohama, Japan (T.A.); the Department of Pharmaceutical Biochemistry, Kumamoto University, Kumamoto, Japan (Y.S.); Cardiovascular Research Institute, Kurume University, Kurume, Japan (H.A.); and the Department of Pharmacology, Kansai Medical University, Osaka, Japan (T.N.).
前列腺素E2 (PGE2) 信号通过降解酸氧化酶 (LOX) 蛋白质来抑制动脉管 (DA) 中的弹性纤维形成,这是建立成人循环的关键步骤.
科学领域:
- 血管生物学 血管生物学
- 发育生物学 发展生物学
- 生物化学 生物化学
背景情况:
- 在胎儿发育过程中,弹性纤维的形成对大动脉弹性至关重要.
- 动脉管道 (DA) 显示弹性生成减少,促进出生后的关闭.
- 抑制DA弹性生成的分子机制在很大程度上是未知的.
研究的目的:
- 研究调节血管管道中弹性生成的分子机制.
- 了解前列腺素E2 (PGE2) 信号在DA发展中的作用.
- 确定参与DA和大动脉之间差异性弹性纤维形成的关键蛋白质.
主要方法:
- 研究了前列腺素E2 (PGE2) 受体EP4在动脉管 (DA) 和大动脉光滑肌细胞 (SMC) 中的信号传递.
- 在DA SMC中利用了腺病毒介导的 lysyl氧化酶 (LOX) 的过度表达.
- 检查了EP4淘汰赛小鼠,并分析了人类DA和大动脉组织.
- 研究了PGE2-EP4-c-Src-脂酶C (PLC) γ信号通路.
主要成果:
- 前列腺素E2 (PGE2) 受体EP4刺激抑制了DA SMCs的弹性生成和降低了lysyl氧化酶 (LOX),但不是大动脉SMCs.
- 过度表达的LOX在DA SMC中挽救了EP4介导的弹性生成抑制.
- 输出EP4的小鼠表现出DA,具有类似于大动脉的弹性特性.
- 人体组织显示弹性纤维形成,EP4和LOX表达之间的反向相关性.
- PGE2-EP4-c-Src-PLCγ通路可能会促进LOX lysosomal降解.
结论:
- 通过EP4发出前列腺素E2 (PGE2) 信号,通过促进LOX降解来抑制DA中的弹性生成.
- 在DA中的弹性生成是由PGE2-EP4信号的空间调节.
- 这种机制对于过渡到成年人循环至关重要.
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