ArticleProceedings of the National Academy of Sciences of the United States of America2010
PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 80 citations in OpenAlex.
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- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
- Cellular and molecular mechanisms of arenobufagin in cancer therapy: a systematic review.Discover oncology · 2025Review
- Targeting PDGF-CC as a promising therapeutic strategy to inhibit cholangiocarcinoma progression.Journal of translational medicine · 2024Article
- Milestones in tumor vascularization and its therapeutic targeting.Nature cancer · 2024Review
- Cancer-associated fibroblasts and its derived exosomes: a new perspective for reshaping the tumor microenvironment.Molecular medicine (Cambridge, Mass.) · 2023Review
- Systemic Cytokines in Retinopathy of Prematurity.Journal of personalized medicine · 2023Review
- Palm Oil Derived Tocotrienol-Rich Fraction Attenuates Vascular Dementia in Type 2 Diabetic Rats.International journal of molecular sciences · 2022Article
- Article
- Transcriptomic analysis of choroidal neovascularization reveals dysregulation of immune and fibrosis pathways that are attenuated by a novel anti-fibrotic treatment.Scientific reports · 2022Article
- Expression and function of PDGF-C in development and stem cells.Open biology · 2021Review
- Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens.Antioxidants (Basel, Switzerland) · 2021Article
- Role of Junctional Adhesion Molecule-C in the Regulation of Inner Endothelial Blood-Retinal Barrier Function.Frontiers in cell and developmental biology · 2021Article
- Platelet-Derived Growth Factor-D Activates Complement System to Propagate Macrophage Polarization and Neovascularization.Frontiers in cell and developmental biology · 2021Article
- Vitreous metabolomics profiling of proliferative diabetic retinopathy.Diabetologia · 2021Article
- Role of METTL3-Dependent NMolecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Platelet-derived growth factor-BB promotes proliferation and migration of retinal microvascular pericytes by up-regulating the expression of C-X-C chemokine receptor types 4.Experimental and therapeutic medicine · 2019Article
- Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model.JCI insight · 2019Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
The importance of identifying VEGF-independent pathways in pathological angiogenesis is increasingly recognized as a result of the emerging drug resistance to anti-VEGF therapies. PDGF-CC is the third member of the PDGF family discovered after more than two decades of studies on PDGF-AA and PDGF-BB. The biological function of PDGF-CC and the underlying cellular and molecular mechanisms remain largely unexplored. Here, using different animal models, we report that PDGF-CC inhibition by neutralizing antibody, shRNA, or genetic deletion suppressed both choroidal and retinal neovascularization. Importantly, we revealed that PDGF-CC targeting acted not only on multiple cell types important for pathological angiogenesis, such as vascular mural and endothelial cells, macrophages, choroidal fibroblasts and retinal pigment epithelial cells, but also on the expression of other important angiogenic genes, such as PDGF-BB and PDGF receptors. At a molecular level, we found that PDGF-CC regulated glycogen synthase kinase (GSK)-3beta phosphorylation and expression both in vitro and in vivo. Activation of GSK3beta impaired PDGF-CC-induced angiogenesis, and inhibition of GSK3beta abolished the antiangiogenic effect of PDGF-CC blockade. Thus, we identified PDGF-CC as an important candidate target gene for antiangiogenic therapy, and PDGF-CC inhibition may be of therapeutic value in treating neovascular diseases.
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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.