ArticleArteriosclerosis, thrombosis, and vascular biology2013
Transcriptome analysis for Notch3 target genes identifies Grip2 as a novel regulator of myogenic response in the cerebrovasculature.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 31 citations in OpenAlex.
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- NOTCH3 limits the epithelial-mesenchymal transition and predicts a favorable clinical outcome in esophageal cancer.Cancer medicine · 2021Article
- The role of Niemann-Pick type C2 in zebrafish embryonic development.Development (Cambridge, England) · 2021Article
- The pericyte: A critical cell in the pathogenesis of CADASIL.Cerebral circulation - cognition and behavior · 2021Review
- Reducing Hypermuscularization of the Transitional Segment Between Arterioles and Capillaries Protects Against Spontaneous Intracerebral Hemorrhage.Circulation · 2020Article
- Investigating diagnostic sequencing techniques for CADASIL diagnosis.Human genomics · 2020Article
- Isolation and differential transcriptome of vascular smooth muscle cells and mid-capillary pericytes from the rat brain.Scientific reports · 2018Article
- Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway.Scientific reports · 2017Article
- Increased Notch3 Activity Mediates Pathological Changes in Structure of Cerebral Arteries.Hypertension (Dallas, Tex. : 1979) · 2017Article
- Homozygous NOTCH3 null mutation and impaired NOTCH3 signaling in recessive early-onset arteriopathy and cavitating leukoencephalopathy.EMBO molecular medicine · 2015Article
- Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Inhibition of Notch signaling facilitates the differentiation of human-induced pluripotent stem cells into neural stem cells.Molecular and cellular biochemistry · 2014Article
- CADASIL and CARASIL.Brain pathology (Zurich, Switzerland) · 2014Review
- Notch signaling functions in retinal pericyte survival.Investigative ophthalmology & visual science · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveNotch3 is critically important for the structure and myogenic response of distal arteries, particularly of cerebral arteries. However, signaling pathways acting downstream of Notch3 remain largely unknown. METHODS AND
resultsTranscriptome analysis using tail arteries of Notch3-null mice identified a core set of 17 novel Notch3-regulated genes confirmed in tail or brain arteries. Postnatal deletion of RBP-Jκ in smooth muscle cells recapitulated the structural, functional, and molecular defects of brain arteries induced by Notch3 deficiency. Transient in vivo blockade of the Notch pathway with γ-secretase inhibitors uncovered, in addition to Notch3, 6 immediate responders, including the voltage-gated potassium channel Kv1.5, which opposes to myogenic constriction of brain arteries, and the glutamate receptor-interacting protein 2 (Grip2) with no previously established role in the cerebrovasculature. We identified a vascular smooth muscle cell isoform of Grip2. We showed that Notch3-RBP-Jκ specifically regulates this isoform. Finally, we found that cerebral arteries of Grip2 mutant mice, which express an N-terminally truncated Grip2 protein, exhibited selective attenuation of pressure-induced contraction.
conclusionsOur data provide insight into how Notch3 signals in the brain arteries, establishing the postnatal requirement of smooth muscle RBP-Jκ in this context. Notch3-regulated transcriptome provides potential for modulating myogenic response in the cerebrovasculature.
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