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Sökning: onr:"swepub:oai:DiVA.org:uu-130834" > PDGF-CC blockade in...

PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets

Hou, Xu (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Kumar, Anil (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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
Arjunan, Pachiappan (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Dong, Lijin (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Maminishkis, Arvydas (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Tang, Zhongshu (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Li, Yang (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Zhang, Fan (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Zhang, Shi-Zhuang (författare)
Department of Radiology, Medical Imaging Centre of the Affiliated Hospital, Weifang Medical University, Weifang 261042, China
Wardega, Piotr (författare)
Uppsala universitet,Ludwiginstitutet för cancerforskning
Chakrabarty, Sagarika (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Liu, Baoying (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Wu, Zhijian (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Colosi, Peter (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Fariss, Robert N (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Lennartsson, Johan (författare)
Uppsala universitet,Ludwiginstitutet för cancerforskning
Nussenblatt, Robert (författare)
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Gutkind, J Silvio (författare)
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
Cao, Yihai (författare)
Karolinska Institutet
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.
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:
http://www.pnas.org/...
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https://urn.kb.se/re...
https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
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

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