在视网膜血管生成和血视网膜屏障形成中,FOXC1调节内皮CD98 (LAT1/4F2hc) 表达
Teena Bhakuni1, Pieter R Norden1, Naoto Ujiie1
1Department of Medicine, Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Nature communications
|May 16, 2024
概括
FOXC1对于视网膜血管生成至关重要,调节氨基酸运输和mTOR活动. 恢复FOXC1功能有助于治疗视网膜血管疾病.
科学领域:
- 血管生物学 血管生物学
- 分子遗传学 分子遗传学
- 眼科医生 眼科 眼科
背景情况:
- 血管新生对于器官发育至关重要,但其转录控制尚未完全理解.
- FOXC1在血管形成中的作用,特别是视网膜中的作用,基本上尚未被探索.
研究的目的:
- 调查FOXC1在调节视网膜血管生成中的重要作用.
- 阐明FOXC1控制血管生长和功能的分子机制.
主要方法:
- 利用内皮细胞特异性的Foxc1淘汰赛小鼠模型.
- 分析了氨基酸载体 (Slc3a2,Slc7a5) 和mTOR通路活性的基因表达.
- 研究了FOXC1在氧气诱导视网膜病变的小鼠模型中的作用.
主要成果:
- 内皮细胞特定的Foxc1损失显著损害了视网膜血管生长.
- 福克斯c1缺乏减少了氨基酸载体Slc3a2和Slc7a5的表达,影响了mTOR信号传递.
- 施用mTOR激动剂挽救了血管性缺陷,FOXC1对于重血管化和解决新血管是至关重要的.
结论:
- FOXC1是视网膜血管生成的关键转录调节器.
- FOXC1通过调节氨基酸运输和mTOR信号传递来控制视网膜血管发育.
- 向FOXC1为视网膜血管疾病提供了潜在的治疗策略.
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