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PDGF-CC blockade in...
PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets
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- Hou, Xu (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Kumar, Anil (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Lee, Chunsik (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Wang, Bin (författare)
- Department of Radiology, Medical Imaging Centre of the Affiliated Hospital, Weifang Medical University, Weifang 261042, China
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- Arjunan, Pachiappan (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Dong, Lijin (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Maminishkis, Arvydas (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Tang, Zhongshu (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Li, Yang (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Zhang, Fan (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Zhang, Shi-Zhuang (författare)
- Department of Radiology, Medical Imaging Centre of the Affiliated Hospital, Weifang Medical University, Weifang 261042, China
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- Wardega, Piotr (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Chakrabarty, Sagarika (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Liu, Baoying (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Wu, Zhijian (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Colosi, Peter (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Fariss, Robert N (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Lennartsson, Johan (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Nussenblatt, Robert (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Gutkind, J Silvio (författare)
- Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
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- Cao, Yihai (författare)
- Karolinska Institutet
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- Li, Xuri (författare)
- National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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(creator_code:org_t)
- 2010-06-21
- 2010
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:27, s. 12216-12221
- Relaterad länk:
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http://www.pnas.org/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- choroidal neovascularization
- glycogen synthase kinase-3 beta
- vascular biology
- retinal neovascularization
- ocular disease
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Hou, Xu
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Kumar, Anil
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Lee, Chunsik
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Wang, Bin
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Arjunan, Pachiap ...
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Dong, Lijin
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Maminishkis, Arv ...
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Tang, Zhongshu
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Li, Yang
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Zhang, Fan
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Zhang, Shi-Zhuan ...
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Wardega, Piotr
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Chakrabarty, Sag ...
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Liu, Baoying
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Wu, Zhijian
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Colosi, Peter
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Fariss, Robert N
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Lennartsson, Joh ...
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Nussenblatt, Rob ...
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Gutkind, J Silvi ...
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Cao, Yihai
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Li, Xuri
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- Artiklar i publikationen
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Proceedings of t ...
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet