Platelet-derived Growth Factor-DD Targeting Arrests Pathological Angiogenesis by Modulating Glycogen Synthase Kinase-3beta Phosphorylation

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Mar 17

PMID 20231273

Citations 19

Authors

Anil Kumar

Xu Hou

Chunsik Lee

Yang Li

Arvydas Maminishkis

Zhongshu Tang

Fan Zhang

Harald F Langer

Pachiappan Arjunan

Lijin Dong

Zhijian Wu

Linda Y Zhu

Lianchun Wang

Wang Min

Peter Colosi

Triantafyllos Chavakis

Xuri Li

Affiliations

Soon will be listed here.

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-3beta (GSK3beta) Ser(9) phosphorylation and Tyr(216) dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3beta activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3beta 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.

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References

Zhang F, Tang Z, Hou X, Lennartsson J, Li Y, Koch A . VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis. Proc Natl Acad Sci U S A. 2009; 106(15):6152-7. PMC: 2669337. DOI: 10.1073/pnas.0813061106. View

Stahl A, Paschek L, Martin G, Feltgen N, Hansen L, Agostini H . Combinatory inhibition of VEGF and FGF2 is superior to solitary VEGF inhibition in an in vitro model of RPE-induced angiogenesis. Graefes Arch Clin Exp Ophthalmol. 2009; 247(6):767-73. DOI: 10.1007/s00417-009-1058-x. View

Economopoulou M, Langer H, Celeste A, Orlova V, Choi E, Ma M . Histone H2AX is integral to hypoxia-driven neovascularization. Nat Med. 2009; 15(5):553-8. PMC: 2713773. DOI: 10.1038/nm.1947. View

Ferrara N . Vascular endothelial growth factor. Arterioscler Thromb Vasc Biol. 2009; 29(6):789-91. DOI: 10.1161/ATVBAHA.108.179663. View

Carmeliet P, De Smet F, Loges S, Mazzone M . Branching morphogenesis and antiangiogenesis candidates: tip cells lead the way. Nat Rev Clin Oncol. 2009; 6(6):315-26. DOI: 10.1038/nrclinonc.2009.64. View

Avci B, Avci R, Inan U, Kaderli B . Comparative evaluation of apoptotic activity in photoreceptor cells after intravitreal injection of bevacizumab and pegaptanib sodium in rabbits. Invest Ophthalmol Vis Sci. 2009; 50(7):3438-46. DOI: 10.1167/iovs.08-2871. View

Mochimaru H, Takahashi E, Tsukamoto N, Miyazaki J, Yaguchi T, Koto T . Involvement of hyaluronan and its receptor CD44 with choroidal neovascularization. Invest Ophthalmol Vis Sci. 2009; 50(9):4410-5. DOI: 10.1167/iovs.08-3044. View

DeNiro M, Alsmadi O, Al-Mohanna F . Modulating the hypoxia-inducible factor signaling pathway as a therapeutic modality to regulate retinal angiogenesis. Exp Eye Res. 2009; 89(5):700-17. DOI: 10.1016/j.exer.2009.06.013. View

Wagsater D, Zhu C, Bjorck H, Eriksson P . Effects of PDGF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression. Atherosclerosis. 2008; 202(2):415-23. DOI: 10.1016/j.atherosclerosis.2008.04.050. View

10.

Spilsbury K, Garrett K, Shen W, Constable I, Rakoczy P . Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization. Am J Pathol. 2000; 157(1):135-44. PMC: 1850220. DOI: 10.1016/S0002-9440(10)64525-7. View

11.

Molander C, Kallin A, Izumi H, Ronnstrand L, Funa K . TNF-alpha suppresses the PDGF beta-receptor kinase. Exp Cell Res. 2000; 258(1):65-71. DOI: 10.1006/excr.2000.4917. View

12.

Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin C . PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol. 2001; 3(5):512-6. DOI: 10.1038/35074588. View

13.

LaRochelle W, Jeffers M, McDonald W, Chillakuru R, Giese N, Lokker N . PDGF-D, a new protease-activated growth factor. Nat Cell Biol. 2001; 3(5):517-21. DOI: 10.1038/35074593. View

14.

Nishijima K, Ng Y, Zhong L, Bradley J, Schubert W, Jo N . Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol. 2007; 171(1):53-67. PMC: 1941589. DOI: 10.2353/ajpath.2007.061237. View

15.

Shojaei F, Wu X, Malik A, Zhong C, Baldwin M, Schanz S . Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol. 2007; 25(8):911-20. DOI: 10.1038/nbt1323. View

16.

Choi S, Kang Y, Jang H, Shin H, Kim H, Kim H . Involvement of glycogen synthase kinase-3beta in palmitate-induced human umbilical vein endothelial cell apoptosis. J Vasc Res. 2007; 44(5):365-74. DOI: 10.1159/000102321. View

17.

Uutela M, Wirzenius M, Paavonen K, Rajantie I, He Y, Karpanen T . PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis. Blood. 2004; 104(10):3198-204. DOI: 10.1182/blood-2004-04-1485. View

18.

Wang Z, Kong D, Banerjee S, Li Y, Adsay N, Abbruzzese J . Down-regulation of platelet-derived growth factor-D inhibits cell growth and angiogenesis through inactivation of Notch-1 and nuclear factor-kappaB signaling. Cancer Res. 2007; 67(23):11377-85. DOI: 10.1158/0008-5472.CAN-07-2803. View

19.

Li R, Maminishkis A, Wang F, Miller S . PDGF-C and -D induced proliferation/migration of human RPE is abolished by inflammatory cytokines. Invest Ophthalmol Vis Sci. 2007; 48(12):5722-32. DOI: 10.1167/iovs.07-0327. View

20.

Andreoli C, Miller J . Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr Opin Ophthalmol. 2007; 18(6):502-8. DOI: 10.1097/ICU.0b013e3282f0ca54. View