期刊
PLOS ONE
卷 9, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0100359
关键词
-
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [2430195, 25126706, 25670382]
- Ono Medical Research Foundation
- Uehara Memorial Foundation
- NOVARTIS Foundation for the Promotion Science
- Japan Diabetes Foundation
- SENSHIN Medical Research Foundation
- Takeda Science Foundation
- Mitsubishi Pharma Research Foundation
- Takeda Medical Research Foundation
- SUZUKEN Memorial Foundation
- Japan Heart Foundation & Astellas/Pfizer Grant for Research on Atherosclerosis Update
- Japan Heart Foundation Dr. Hiroshi Irisawa & Dr. Aya Irisawa Memorial Research Grant
- Grants-in-Aid for Scientific Research [25670382, 26115008, 24390195] Funding Source: KAKEN
Evolutionarily conserved Notch signaling controls cell fate determination and differentiation during development, and is also essential for neovascularization in adults. Although recent studies suggest that the Notch pathway is associated with age-related conditions, it remains unclear whether Notch signaling is involved in vascular aging. Here we show that Notch signaling has a crucial role in endothelial cell senescence. Inhibition of Notch signaling in human endothelial cells induced premature senescence via a p16-dependent pathway. Conversely, over-expression of Notch1 or Jagged1 prolonged the replicative lifespan of endothelial cells. Notch1 positively regulated the expression of inhibitor of DNA binding 1 (Id1) and MAP kinase phosphatase 1 (MKP1), while MKP1 further up-regulated Id1 expression by inhibiting p38MAPK-induced protein degradation. Over-expression of Id1 down-regulated p16 expression, thereby inhibiting premature senescence of Notch1-deleted endothelial cells. These findings indicate that Notch1 signaling has a role in the regulation of endothelial cell senescence via a p16-dependent pathway and suggest that activation of Notch1 could be a new therapeutic target for treating age-associated vascular diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据