Platelet-derived growth factor-DD targeting arrests pathological angiogenesis by modulating glycogen synthase kinase-3β phosphorylation
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role of PDGF-DD in pathological angiogenesis and the underlying cellular and molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that PDGF-DD expression was up-regulated during pathological angiogenesis, and inhibition of PDGF-DD suppressed both choroidal and retinal neovascularization. We also demonstrated a novel mechanism mediating the function of PDGF-DD. PDGF-DD induced glycogen synthase kinase-3β (GSK3β) Ser9 phosphorylation and Tyr216 dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3β activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3β and many other genes important for angiogenesis and apoptosis. Thus, we identified PDGF-DD as an important target gene for antiangiogenic therapy due to its pleiotropic effects on vascular and non-vascular cells. PDGF-DD inhibition may offer new therapeutic options to treat neovascular diseases.
Details
Original language | English |
---|---|
Pages (from-to) | 15500-15510 |
Number of pages | 11 |
Journal | Journal of Biological Chemistry |
Volume | 285 |
Issue number | 20 |
Publication status | Published - 14 May 2010 |
Peer-reviewed | Yes |
Externally published | Yes |
External IDs
researchoutputwizard | legacy.publication#36905 |
---|---|
Scopus | 77952056907 |
PubMed | 20231273 |