在毛细血管形中,MAPK信号传递和 ангиопоэтин-2 有助于内皮通透性
Sana Nasim1,2, Mariam Baig1, Jill Wylie-Sears1
1Vascular Biology Program, Boston Children's Hospital, Boston, MA 02115.
概括
毛细血管形 (CM) 涉及由于GNAQ p.R183Q突变的血管透性增加. 针对angiopoietin-2和MAPK/ERK信号通路可以恢复CM中的内皮屏障.
科学领域:
- 血管生物学 血管生物学
- 遗传学 是一个遗传学.
- 皮肤病学 皮肤病学
背景情况:
- 非综合性毛细血管形 (CM) 主要影响皮肤.
- 斯特-韦伯综合征 (SWS) 涉及皮肤,大脑瘤和眼睛的肌.
- 在GNAQ p.R183Q体质突变导致超过90%的CM.
研究的目的:
- 调查CM.血管透性增加的机制.
- 探索潜在的治疗点,以恢复CM的内皮屏障.
主要方法:
- 使用具有GNAQ p.R183Q (EC-R183Q) 的内皮细胞进行超内皮电阻 (TEER) 测定.
- 在Gnaq p.R183Q小鼠模型中的验证.
- 研究了血管蛋白-2 (ANGPT2) 和MAPK/ERK信号传递的作用.
主要成果:
- 与野生类型内皮细胞相比,EC-R183Q的通透性显著增加.
- 在Gnaq p.R183Q小鼠模型中证实了血管透率的增加.
- 抑制ANGPT2和MEK1,2抑制剂治疗部分恢复了EC屏障,结合时具有添加效应.
结论:
- 具有GNAQ p.R183Q突变的内皮细胞表现出增加的透性,表明CM中的内皮屏障受损.
- ANGPT2和MAPK/ERK信号通路与CM.的内皮屏障功能障碍有关.
- 对ANGPT2和MAPK/ERK通路的联合向为CM提供了潜在的治疗策略.
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