ArticleCell death & disease2014
Nox4 and redox signaling mediate TGF-β-induced endothelial cell apoptosis and phenotypic switch.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 84 citations in OpenAlex.
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- Lung Microphysiological System Validates Novel Cell Therapy for Acute Respiratory Distress Syndrome.Advanced biology · 2026Article
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Revisiting ROS: duality in organ aging progression.Molecular biology reports · 2025Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- The Vascular Function of Resistance Arteries Depends on NADPH Oxidase 4 and Is Exacerbated by Perivascular Adipose Tissue.Antioxidants (Basel, Switzerland) · 2024Article
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Role of NADPH Oxidase 4 in Corneal Endothelial Cells Is Mediated by Endoplasmic Reticulum Stress and Autophagy.Antioxidants (Basel, Switzerland) · 2023Article
- Endothelial cell cycle state determines propensity for arterial-venous fate.Nature communications · 2022Article
- Reduced phagocytosis, ROS production and enhanced apoptosis of leukocytes upon alcohol drinking in healthy volunteers.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2022Article
- Targeting fibrosis, mechanisms and cilinical trials.Signal transduction and targeted therapy · 2022Review
- Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications.Frontiers in bioengineering and biotechnology · 2022Review
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Microvascular significance of TGF-β axis activation in COVID-19.Frontiers in cardiovascular medicine · 2022Review
- Redox Dysregulation in Aging and COPD: Role of NOX Enzymes and Implications for Antioxidant Strategies.Antioxidants (Basel, Switzerland) · 2021Review
- Phosphorylation inhibition of protein-tyrosine phosphatase 1B tyrosine-152 induces bone regeneration coupled with angiogenesis for bone tissue engineering.Bioactive materials · 2021Article
- NOX4 regulates macrophage apoptosis resistance to induce fibrotic progression.The Journal of biological chemistry · 2021Article
- TGF Beta Induces Vitamin D Receptor and Modulates Mitochondrial Activity of Human Pancreatic Cancer Cells.Cancers · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGF-β) triggers apoptosis in endothelial cells, while the mechanisms underlying this action are not entirely understood. Using genetic and pharmacological tools, we demonstrated that TGF-β induced a moderate apoptotic response in human cultured endothelial cells, which was dependent upon upregulation of the Nox4 NADPH oxidase and production of reactive oxygen species (ROS). In contrast, we showed that ectopic expression of Nox4 via viral vectors (vNox4) produced an antiapoptotic effect. TGF-β caused ROS-dependent p38 activation, whereas inhibition of p38 blunted TGF-β-induced apoptosis. However, vNox4, but not TGF-β, activated Akt, and inhibition of Akt attenuated the antiapoptotic effect of vNox4. Akt activation induced by vNox4 was accompanied by inactivation of the protein tyrosine phosphatase-1B (PTP1B) function and enhanced vascular endothelial growth factor receptor (VEGFR)-2 phosphorylation. Moreover, we showed that TGF-β enhanced Notch signaling and increased expression of the arterial marker EphrinB2 in a redox-dependent manner. In summary, our results suggest that Nox4 and ROS have pivotal roles in mediating TGF-β-induced endothelial apoptosis and phenotype specification. Redox mechanisms may influence endothelial cell functions by modulating p38, PTP1B/VEGFR/Akt and Notch signaling pathways.
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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.