ArticleCirculation research2013
A receptor-specific function for Notch2 in mediating vascular smooth muscle cell growth arrest through cyclin-dependent kinase inhibitor 1B.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Single-cell transcriptomics reveals cell-type-specific circadian rhythms and their disruption by acute misalignment in mouse aorta.bioRxiv : the preprint server for biology · 2026Article
- Hepatic factor MANF drives hepatocytes reprogramming by detaining cytosolic CK19 in intrahepatic cholangiocarcinoma.Cell death and differentiation · 2025Article
- The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner.Journal of virology · 2024Article
- Clinical and Genetic Characteristics of Alagille Syndrome in Adults.Journal of clinical and translational hepatology · 2023Article
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- Inhibition of tiRNA-Gly-GCC ameliorates neointimal formationFrontiers in cardiovascular medicine · 2023Article
- Notch Signaling in Vascular Endothelial and Mural Cell Communications.Cold Spring Harbor perspectives in medicine · 2022Article
- Notch signalling in healthy and diseased vasculature.Open biology · 2022Review
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- Notch signaling regulates strain-mediated phenotypic switching of vascular smooth muscle cells.Frontiers in cell and developmental biology · 2022Article
- Smooth Muscle Cell Notch2 Is Not Required for Atherosclerotic Plaque Formation in ApoE Null Mice.Journal of vascular research · 2022Article
- Single-cell transcriptomics of murine mural cells reveals cellular heterogeneity.Science China. Life sciences · 2021Article
- Adding a "Notch" to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach.Frontiers in cell and developmental biology · 2021Review
- Notch3 in Development, Health and Disease.Biomolecules · 2020Review
- Transcriptomic profiling of experimental arterial injury reveals new mechanisms and temporal dynamics in vascular healing response.JVS-vascular science · 2020Article
- The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS.Journal of translational medicine · 2019Article
- Characterization of smooth muscle cells from human atherosclerotic lesions and their responses to Notch signaling.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- The pathophysiological basis of vascular disease.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Endothelial cell-induced cytoglobin expression in vascular smooth muscle cells contributes to modulation of nitric oxide.Vascular pharmacology · 2018Article
- Notch2 and Proteomic Signatures in Mouse Neointimal Lesion Formation.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationaleDeregulated vascular smooth muscle cell (VSMC) proliferation contributes to multiple vascular pathologies, and Notch signaling regulates VSMC phenotype.
objectivePrevious work focused on Notch1 and Notch3 in VSMC during vascular disease; however, the role of Notch2 is unknown. Because injured murine carotid arteries display increased Notch2 in VSMC as compared with uninjured arteries, we sought to understand the impact of Notch2 signaling in VSMCs. METHODS AND
resultsIn human primary VSMCs, Jagged-1 (Jag-1) significantly reduced proliferation through specific activation of Notch2. Increased levels of p27(kip1) were observed downstream of Jag-1/Notch2 signaling and were required for cell cycle exit. Jag-1 activation of Notch resulted in increased phosphorylation on serine 10, decreased ubiquitination, and prolonged half-life of p27(kip1). Jag-1/Notch2 signaling robustly decreased S-phase kinase-associated protein, an F-box protein that degrades p27(kip1) during G1. Overexpression of S-phase kinase-associated protein before Notch activation by Jag-1 suppressed the induction of p27(kip1). Additionally, increased Notch2 and p27(kip1) expression was colocalized to the nonproliferative zone of injured arteries as indicated by co-staining with proliferating cell nuclear antigen, whereas Notch3 was expressed throughout normal and injured arteries, suggesting Notch2 may negatively regulate lesion formation.
conclusionsWe propose a receptor-specific function for Notch2 in regulating Jag-1-induced p27(kip1) expression and growth arrest in VSMCs. During vascular remodeling, colocalization of Notch2 and p27(kip1) to the nonproliferating region supports a model where Notch2 activation may negatively regulate VSMC proliferation to lessen the severity of the lesion. Thus, Notch2 is a potential target for control of VSMC hyperplasia.
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