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Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells.
Open accessAbstract
Transforming growth factor beta (TGF-beta) is a multifunctional polypeptide that regulates the proliferation and differentiation of various cells and has an angiogenic effect in vivo, although it inhibits the growth of cultured endothelial cells. We report here that TGF-beta treatment of quiescent cultures of mouse embryo-derived AKR-2B cells, which are growth-stimulated by TGF-beta, and human lung adenocarcinoma A549 cells, which are growth-inhibited by TGF-beta, results in the induction of vascular endothelial growth factor (VEGF) mRNA and protein. Maximal VEGF mRNA levels occurred 4-8 h after stimulation with a decline to background levels in 24 h. In contrast, the related placenta growth factor mRNA was not induced by TGF-beta in these cells. No VEGF receptor mRNA was seen in AKR-2B cells. Also, TGF-beta treatment of endothelial cells, which express the FLT1 and KDR/FLK-1 receptors for VEGF, did not cause VEGF induction. Because VEGF is known to be a strong angiogenic factor for endothelial cells, the results suggest that the angiogenic effect of TGF-beta on endothelial cells in blood vessels may be mediated at least partly by a paracrine induction of VEGF in other surrounding cell types.
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“Pro-angiogenic activities of TGF-β on endothelial cells are mediated by the ALK1 type I receptor and endoglin, which promote endothelial cell proliferation and migration265”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [265]
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“Various observations highlight activities of TGF-β on endothelial cells that may promote or repress angiogenesis, depending on the experimental setting264–266.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [265]
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Metadata
- Authors
- Pertovaara, L., Kaipainen, A., Mustonen, T., Orpana, A., Ferrara, N., Saksela, O., & Alitalo, K.
- Affiliations
- University of Helsinki (FI)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-03
- Volume
- 269
- Issue
- 9
- Pages
- 6271-6274
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1494416455
- Cited by
- 694
- References
- 38
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 11 · 2016: 9 · 2015: 13 · 2014: 20 · 2013: 16 · 2012: 25
- FWCI
- 10.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- vascular endothelial growth factor, TGF-beta, angiogenesis, paracrine signaling, placental growth factor, VEGF receptors, Flt-1, KDR/Flk-1, A549 cells, lung adenocarcinoma, endothelial cells, fibroblasts, epithelial cells, VEGF mRNA expression
- MeSH terms
- Animals, Cattle, Cell Line, Cells, Cultured, Endothelium, Vascular, Epithelium, Fibroblasts, Humans, Hybrid Cells, Lung Neoplasms, Lymphokines, Mice, Inbred AKR, Recombinant Proteins, Tumor Cells, Cultured, Umbilical Veins, Immunoblotting, Transforming Growth Factor beta, Endothelial Growth Factors, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice
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