ArticleNature metabolism2022
The endothelial Dll4-muscular Notch2 axis regulates skeletal muscle mass.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Mechanisms of Impaired Skeletal Muscle Regeneration and Therapeutic Approaches in Aging and Chronic Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Deficiency of muscular dystrophy-related gene JAG2 causes NOTCH signaling dysfunction in muscle stem cells.The Journal of clinical investigation · 2026Article
- Sarcopenia promotes tumorigenesis by disrupting NOTCH-SDC2-regulated biogenesis of muscle-derived extracellular vesicles.Nature communications · 2026Article
- Endothelial cystathionine-γ-lyase (CTH) regulates body weight and insulin resistance in mice fed a high-fat diet.Redox biology · 2026Article
- 0.33Science advances · 2026Article
- Bidirectional Regulation between Metabolic Dysfunction-associated Steatotic Liver Disease and Sarcopenia via Liver-muscle Crosstalk.Journal of clinical and translational hepatology · 2026Article
- Notch2 Directs aTreg Cell Fate Toward Immunoregulation or Inflammatory Pyroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Signaling networks governing skeletal muscle growth, atrophy, and cachexiaSkeletal muscle · 2025Review
- Muscle-specific increased expression ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Iron supplementation alleviates pathologies in a mouse model of facioscapulohumeral muscular dystrophy.The Journal of clinical investigation · 2025Article
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Introduction to the CLEM technique developed in the field of neuroanatomy.Anatomical science international · 2025Article
- Combined effects of mechanical overload and high-intensity interval training on skeletal muscle hypertrophy in male mice.Physiological reports · 2025Article
- Key genes and processes affected by atorvastatin treatment in mouse diaphragm muscle.Archives of toxicology · 2025Article
- Article
- Kdm2a inhibition in skeletal muscle improves metabolic flexibility in obesity.Nature metabolism · 2025Article
- Metabolic and molecular regulation in skeletal muscle dysfunction and regeneration.Frontiers in cell and developmental biology · 2025Review
- Molecular mechanism of skeletal muscle loss and its prevention by natural resources.Food science and biotechnology · 2024Review
- Time-series transcriptomics reveals distinctive mRNA expression dynamics associated with gene ontology specificity and protein expression in skeletal muscle after electrical stimulation-induced resistance exercise.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- KLF13 restrains Dll4-muscular Notch2 axis to improve the muscle atrophy.Journal of cachexia, sarcopenia and muscle · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Adult skeletal muscle is a highly plastic tissue that readily reduces or gains its mass in response to mechanical and metabolic stimulation; however, the upstream mechanisms that control muscle mass remain unclear. Notch signalling is highly conserved, and regulates many cellular events, including proliferation and differentiation of various types of tissue stem cell via cell-cell contact. Here we reveal that multinucleated myofibres express Notch2, which plays a crucial role in disuse- or diabetes-induced muscle atrophy. Mechanistically, in both atrophic conditions, the microvascular endothelium upregulates and releases the Notch ligand, Dll4, which then activates muscular Notch2 without direct cell-cell contact. Inhibition of the Dll4-Notch2 axis substantively prevents these muscle atrophy and promotes mechanical overloading-induced muscle hypertrophy in mice. Our results illuminate a tissue-specific function of the endothelium in controlling tissue plasticity and highlight the endothelial Dll4-muscular Notch2 axis as a central upstream mechanism that regulates catabolic signals from mechanical and metabolic stimulation, providing a therapeutic target for muscle-wasting diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.