ArticleAngiogenesis2012
Over-expression of BMP4 inhibits experimental choroidal neovascularization by modulating VEGF and MMP-9.
Article in Angiogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- MMP9 Genotype and Systemic T-Cell Subsets Correlate With Structural and Functional Outcomes in Neovascular Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2026Article
- Unraveling the therapeutic landscape of miRNAs in pancreatic cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Bone morphogenetic proteins (BMPs) at the forefront of ocular diseases and therapeutics.Eye and vision (London, England) · 2025Review
- Chrdl1-mediated BMP4 inhibition disrupts the balance between retinal neurons and Müller Glia.Cell death discovery · 2024Article
- Endothelial SMAD1/5 signaling couples angiogenesis to osteogenesis in juvenile bone.Communications biology · 2024Article
- Loss of Bone Morphogenetic Protein-9 Reduces Survival and Increases MMP Activity After Myocardial Infarction.JACC. Basic to translational science · 2023Article
- Neovascular Progression and Retinal Dysfunction in the Laser-Induced Choroidal Neovascularization Mouse Model.Biomedicines · 2023Article
- Evidence of vascular involvement in myopia: a review.Frontiers in medicine · 2023Review
- Article
- Review
- The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms.International journal of molecular sciences · 2022Review
- Bone Morphogenetic Proteins and Diabetic Retinopathy.Biomolecules · 2021Review
- Innate Immunity in Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2021Article
- Matrix Metalloproteinases in Age-Related Macular Degeneration (AMD).International journal of molecular sciences · 2020Review
- Prognostic Significance of Lymphocyte Infiltration and a Stromal Immunostaining of a Bladder Cancer Associated Diagnostic Panel in Urothelial Carcinoma.Diagnostics (Basel, Switzerland) · 2019Article
- MicroRNA let-7a regulates angiogenesis by targeting TGFBR3 mRNA.Journal of cellular and molecular medicine · 2019Article
- The Controversial Role of TGF-β in Neovascular Age-Related Macular Degeneration Pathogenesis.International journal of molecular sciences · 2018Review
- Increased susceptibility to fundus camera-delivered light-induced retinal degeneration in mice deficient in oxidative stress response proteins.Experimental eye research · 2017Article
- Endothelial follistatin-like-1 regulates the postnatal development of the pulmonary vasculature by modulating BMP/Smad signaling.Pulmonary circulation · 2017Article
- Role of ID Proteins in BMP4 Inhibition of Profibrotic Effects of TGF-β2 in Human TM Cells.Investigative ophthalmology & visual science · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Bone morphorgenetic protein (BMP)-4 has been shown to play a pivotal role in eye development; however, its role in mature retina or ocular angiogenic diseases is unclear. Activating downstream Smad signaling, BMP4 can be either pro-angiogenic or anti-angiogenic, depending on the context of cell types and associated microenvironment. In this study, we generated transgenic mice over-expressing BMP4 in retinal pigment epithelial (RPE) cells (Vmd2-Bmp4 Tg mice), and used the laser-induced choroidal neovascularization (CNV) model to study the angiogenic properties of BMP4 in adult eyes. Vmd2-Bmp4 Tg mice displayed normal retinal histology at 10 weeks of age when compared with age-matched wildtype mice. Over-expression of BMP4 in RPE in the transgenic mice was confirmed by real-time PCR and immunostaining. Elevated levels of Smad1,5 phosphorylation were found in BMP4 transgenic mice compared to wildype mice. Over-expression of BMP4 was associated with less severe CNV as characterized by fluorescein angiography, CNV volume measurement and histology. While control mice showed increased levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 after laser injury, Vmd2-Bmp4 Tg showed no increase in either VEGF or MMP-9. Further, we found that TNF-induced MMP-9 secretion in vitro was reduced by pretreatment of RPE cells with BMP4. The inhibition of MMP-9 was Smad-dependent because BMP4 failed to repress TNF-induced MMP-9 expression when Smad1,5 was silenced by siRNA. In summary, our studies identified an anti-angiogenic role for BMP4 in laser-induced CNV, mediated by direct inhibition of MMP-9 and indirect inhibition of VEGF.
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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.