ArticleFrontiers in immunology2023
Inhibition of the intracellular domain of Notch1 results in vascular endothelial cell dysfunction in sepsis.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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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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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- New trends and hotspots in sepsis-related protein post-translational modification: a bibliometric and visual analysis.Frontiers in medicine · 2025Pooled it
- Endothelial USP8 is essential for angiogenesis.Angiogenesis · 2026Article
- Targeting the lactylation of ENO1 alleviates endothelial dysfunction in sepsis.Clinical and translational medicine · 2026Article
- Macrophage Notch1 drives septic cardiac dysfunction by impairing mitophagy and promoting NLRP3 activation.Biology direct · 2025Article
- Ubiquitin-specific protease: an emerging key player in cardiomyopathy.Cell communication and signaling : CCS · 2025Review
- Andrographolide ameliorates sepsis-induced acute liver injury by attenuating endoplasmic reticulum stress through the FKBP1A-mediated NOTCH1/AK2 pathway.Cell biology and toxicology · 2025Article
- Melatonin Exerts Positive Effects on Sepsis Through Various Beneficial Mechanisms.Drug design, development and therapy · 2025Review
- Barrier genes are associated with preterm birth.Frontiers in medicine · 2025Article
- Notch transcriptional target tmtc1 maintains vascular homeostasis.Cellular and molecular life sciences : CMLS · 2024Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Notch signaling is critical for regulating the function of vascular endothelial cells (ECs). However, the effect of the intracellular domain of Notch1 (NICD) on EC injury in sepsis remains unclear. Methods: We established a cell model of vascular endothelial dysfunction and induced sepsis in a mouse model Results: We found that LPS, interleukin 6, and serum collected from septic children could inhibit the expression of NICD and its downstream regulator Hes1, which impaired endothelial barrier function and led to EC apoptosis through the AKT pathway. Mechanistically, LPS decreased the stability of NICD by inhibiting the expression of a deubiquitylating enzyme, ubiquitin-specific proteases 8 (USP8). Melatonin, however, upregulated USP8 expression, thus maintaining the stability of NICD and Notch signaling, which ultimately reduced EC injury in our sepsis model and elevated the survival rate of septic mice. Conclusions: We found a previously uncharacterized role of Notch1 in mediating vascular permeability during sepsis, and we showed that inhibition of NICD resulted in vascular EC dysfunction in sepsis, which was reversed by melatonin. Thus, the Notch1 signaling pathway is a potential target for the treatment of sepsis.
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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.