ArticleCardiovascular research2015
Jagged1 intracellular domain-mediated inhibition of Notch1 signalling regulates cardiac homeostasis in the postnatal heart.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 34 citations in OpenAlex.
- Jagged-1 mutation is associated with congenital heart defects: a case report.Journal of medical case reports · 2026Article
- Review
- AWGE-ESPCA: An edge sparse PCA model based on adaptive noise elimination regularization and weighted gene network for Hermetia illucens genomic data analysis.PLoS computational biology · 2025Article
- Notch signaling pathway and heart development, congenital heart disease, and myocardial regeneration.Frontiers in bioengineering and biotechnology · 2025Review
- NCardiovascular diabetology · 2024Article
- Article
- Omentin-1 drives cardiomyocyte cell cycle arrest and metabolic maturation by interacting with BMP7.Cellular and molecular life sciences : CMLS · 2023Article
- JAG1 Intracellular Domain Enhances AR Expression and Signaling and Promotes Stem-like Properties in Prostate Cancer Cells.Cancers · 2022Article
- Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease.JCI insight · 2022Article
- Article
- Inhibition of the NOTCH1 Pathway in the Stressed Heart Limits Fibrosis and Promotes Recruitment of Non-Myocyte Cells into the Cardiomyocyte Fate.Journal of cardiovascular development and disease · 2022Article
- Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal-dependent and -independent pathways.Development (Cambridge, England) · 2021Article
- Elabela gene therapy promotes angiogenesis after myocardial infarction.Journal of cellular and molecular medicine · 2021Article
- Hepatocyte TLR4 triggers inter-hepatocyte Jagged1/Notch signaling to determine NASH-induced fibrosis.Science translational medicine · 2021Article
- Review
- CircHIPK3 Plays Vital Roles in Cardiovascular Disease.Frontiers in cardiovascular medicine · 2021Review
- Association of Jagged1 expression with malignancy and prognosis in human pancreatic cancer.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a.Molecular therapy. Nucleic acids · 2020Article
- Article
- Jagged1 protein processing in the developing mammalian lens.Biology open · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsNotch1 signalling in the heart is mainly activated via expression of Jagged1 on the surface of cardiomyocytes. Notch controls cardiomyocyte proliferation and differentiation in the developing heart and regulates cardiac remodelling in the stressed adult heart. Besides canonical Notch receptor activation in signal-receiving cells, Notch ligands can also activate Notch receptor-independent responses in signal-sending cells via release of their intracellular domain. We evaluated therefore the importance of Jagged1 (J1) intracellular domain (ICD)-mediated pathways in the postnatal heart. METHODS AND
resultsIn cardiomyocytes, Jagged1 releases J1ICD, which then translocates into the nucleus and down-regulates Notch transcriptional activity. To study the importance of J1ICD in cardiac homeostasis, we generated transgenic mice expressing a tamoxifen-inducible form of J1ICD, specifically in cardiomyocytes. Using this model, we demonstrate that J1ICD-mediated Notch inhibition diminishes proliferation in the neonatal cardiomyocyte population and promotes maturation. In the neonatal heart, a response via Wnt and Akt pathway activation is elicited as an attempt to compensate for the deficit in cardiomyocyte number resulting from J1ICD activation. In the stressed adult heart, J1ICD activation results in a dramatic reduction of the number of Notch signalling cardiomyocytes, blunts the hypertrophic response, and reduces the number of apoptotic cardiomyocytes. Consistently, this occurs concomitantly with a significant down-regulation of the phosphorylation of the Akt effectors ribosomal S6 protein (S6) and eukaryotic initiation factor 4E binding protein1 (4EBP1) controlling protein synthesis.
conclusionsAltogether, these data demonstrate the importance of J1ICD in the modulation of physiological and pathological hypertrophy, and reveal the existence of a novel pathway regulating cardiac homeostasis.
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