ArticleCell death & disease2014
TGF-β/Smad3 inhibit vascular smooth muscle cell apoptosis through an autocrine signaling mechanism involving VEGF-A.
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 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
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- Antagonistic SMAD2/3 control of TIMP-1, VEGF-A, and hypoxia signaling in myofibroblasts shapes histotype-specific angiogenesis in lung cancer.Cell death & disease · 2026Article
- Refining fibroblast-to-cardiomyocyte transdifferentiation protocols to explore emergent self-organization in cardiac cultures.PloS one · 2026Article
- Profiling of main regulators of angiogenesis and inflammation in human PBMC and plasma revealed associations with lower extremity artery disease.Scientific reports · 2025Article
- Role of transforming growth factor-β1 pathway in angiogenesis induced by chronic stress in colorectal cancer.Cancer biology & therapy · 2024Article
- Gliovascular transcriptional perturbations in Alzheimer's disease reveal molecular mechanisms of blood brain barrier dysfunction.Nature communications · 2024Article
- Treatment of neovascular age-related macular degeneration with anti-vascular endothelial growth factor drugs: progress from mechanisms to clinical applications.Frontiers in medicine · 2024Review
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Article
- TGF-β is elevated in hyperuricemic individuals and mediates urate-induced hyperinflammatory phenotype in human mononuclear cells.Arthritis research & therapy · 2023Article
- Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids.International journal of molecular sciences · 2022Article
- Endoglin Modulates TGFβR2 Induced VEGF and Proinflammatory Cytokine Axis Mediated Angiogenesis in Prolonged DEHP-Exposed Breast Cancer Cells.Biomedicines · 2022Article
- Smad2 inhibition ofAtherosclerosis plus · 2021Article
- miR-361-5p Mediates SMAD4 to Promote Porcine Granulosa Cell Apoptosis through VEGFA.Biomolecules · 2020Article
- Hypoxia induces tumor cell growth and angiogenesis in non-small cell lung carcinoma via the Akt-PDK1-HIF1α-YKL-40 pathway.Translational cancer research · 2020Article
- LncRNA TNK2-AS1 regulated ox-LDL-stimulated HASMC proliferation and migration via modulating VEGFA and FGF1 expression by sponging miR-150-5p.Journal of cellular and molecular medicine · 2019Article
- The Role of the miR-21/SPRY2 Axis in Modulating Proangiogenic Factors, Epithelial Phenotypes, and Wound Healing in Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2019Article
- Enhanced TGF-β Signaling Contributes to the Insulin-Induced Angiogenic Responses of Endothelial Cells.iScience · 2019Article
- Systematic Analysis of Transcriptomic Profile of Chondrocytes in Osteoarthritic Knee Using Next-Generation Sequencing and Bioinformatics.Journal of clinical medicine · 2018Article
- TGF-β Signaling in Control of Cardiovascular Function.Cold Spring Harbor perspectives in biology · 2018Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
We have previously shown that in the presence of elevated Smad3, transforming growth factor-β (TGF-β) transforms from an inhibitor to a stimulant of vascular smooth muscle cell (SMC) proliferation and intimal hyperplasia (IH). Here we identify a novel mechanism through which TGF-β/Smad3 also exacerbates IH by inhibiting SMC apoptosis. We found that TGF-β treatment led to inhibition of apoptosis in rat SMCs following viral expression of Smad3. Conditioned media from these cells when applied to naive SMCs recapitulated this effect, suggesting an autocrine pathway through a secreted factor. Gene array of TGF-β/Smad3-treated cells revealed enhanced expression of vascular endothelial growth factor (VEGF), a known inhibitor of endothelial cell apoptosis. We then evaluated whether VEGF is the secreted mediator responsible for TGF-β/Smad3 inhibition of SMC apoptosis. In TGF-β/Smad3-treated cells, VEGF mRNA and protein as well as VEGF secretion were increased. Moreover, recombinant VEGF-A inhibited SMC apoptosis and a VEGF-A-neutralizing antibody reversed the inhibitory effect of conditioned media on SMC apoptosis. Stimulation of SMCs with TGF-β led to the formation of a complex of Smad3 and hypoxia-inducible factor-1α (HIF-1α) that in turn activated the VEGF-A promoter and transcription. In rat carotid arteries following arterial injury, Smad3 and VEGF-A expression were upregulated. Moreover, Smad3 gene transfer further enhanced VEGF expression as well as inhibited SMC apoptosis. Finally, blocking either the VEGF receptor or Smad3 signaling in injured carotid arteries abrogated the inhibitory effect of Smad3 on vascular SMC apoptosis. Taken together, our study reveals that following angioplasty, elevation of both TGF-β and Smad3 leads to SMC secretion of VEGF-A that functions as an autocrine inhibitor of SMC apoptosis. This novel pathway provides further insights into the role of TGF-β in the development of IH.
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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.