JOURNAL BROWSE
Search
Advanced SearchSearch Tips
Loss of phospholipase D2 impairs VEGF-induced angiogenesis
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 49, Issue 3,  2016, pp.191-196
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2016.49.3.219
 Title & Authors
Loss of phospholipase D2 impairs VEGF-induced angiogenesis
Lee, Chang Sup; Ghim, Jaewang; Song, Parkyong; Suh, Pann-Ghill; Ryu, Sung Ho;
  PDF(new window)
 Abstract
Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis and critical for normal embryonic development and repair of pathophysiological conditions in adults. Although phospholipase D (PLD) activity has been implicated in angiogenic processes, its role in VEGF signaling during angiogenesis in mammals is unclear. Here, we found that silencing of PLD2 by siRNA blocked VEGF-mediated signaling in immortalized human umbilical vein endothelial cells (iHUVECs). Also, VEGF-induced endothelial cell survival, proliferation, migration, and tube formation were inhibited by PLD2 silencing. Furthermore, while Pld2-knockout mice exhibited normal development, loss of PLD2 inhibited VEGF-mediated ex vivo angiogenesis. These findings suggest that PLD2 functions as a key mediator in the VEGF-mediated angiogenic functions of endothelial cells.
 Keywords
Angiogenesis;Aorta ring;Endothelial cells;Phospholipase D;Tube formation;VEGF;
 Language
English
 Cited by
1.
Assessment of the anti-metastatic properties of sanguiin H-6 in HUVECs and MDA-MB-231 human breast cancer cells, Bioorganic & Medicinal Chemistry Letters, 2016, 26, 14, 3291  crossref(new windwow)
2.
Abietic acid isolated from pine resin (Resina Pini) enhances angiogenesis in HUVECs and accelerates cutaneous wound healing in mice, Journal of Ethnopharmacology, 2017, 203, 279  crossref(new windwow)
 References
1.
Ferrara N, Gerber HP and LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9, 669-676 crossref(new window)

2.
Olsson AK, Dimberg A, Kreuger J and Claesson-Welsh L (2006) VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 7, 359-371 crossref(new window)

3.
Carmeliet P and Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298-307 crossref(new window)

4.
Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438, 932-936 crossref(new window)

5.
Ribatti D, Nico B and Crivellato E (2009) Morphological and molecular aspects of physiological vascular morphogenesis. Angiogenesis 12, 101-111 crossref(new window)

6.
Behl T and Kotwani A (2015) Exploring the various aspects of the pathological role of vascular endothelial growth factor (VEGF) in diabetic retinopathy. Pharmacol Res 99, 137-148 crossref(new window)

7.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT and De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56, 549-580 crossref(new window)

8.
Frohman MA (2015) The phospholipase D superfamily as therapeutic targets. Trends Pharmacol Sci 36, 137-144 crossref(new window)

9.
Gomez-Cambronero J (2014) Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis. J Biol Chem 289, 22557-22566 crossref(new window)

10.
Jang JH, Lee CS, Hwang D and Ryu SH (2012) Understanding of the roles of phospholipase D and phosphatidic acid through their binding partners. Prog Lipid Res 51, 71-81 crossref(new window)

11.
Nelson RK and Frohman MA (2015) Physiological and Pathophysiological roles for Phospholipase D. J Lipid Res 56, 2229-2237 crossref(new window)

12.
Zhang Q, Wang D, Kundumani-Sridharan V et al (2010) PLD1-dependent PKCgamma activation downstream to Src is essential for the development of pathologic retinal neovascularization. Blood 116, 1377-1385 crossref(new window)

13.
Zeng XX, Zheng X, Xiang Y et al (2009) Phospholipase D1 is required for angiogenesis of intersegmental blood vessels in zebrafish. Dev Biol 328, 363-376 crossref(new window)

14.
Kim JH, Kim HW, Jeon H, Suh PG and Ryu SH (2006) Phospholipase D1 regulates cell migration in a lipase activity-independent manner. J Biol Chem 281, 15747-15756 crossref(new window)

15.
Jenkins GM and Frohman MA (2005) Phospholipase D: a lipid centric review. Cell Mol Life Sci 62, 2305-2316 crossref(new window)

16.
Cockcroft S (2001) Signalling roles of mammalian phospholipase D1 and D2. Cell Mol Life Sci 58, 1674-1687 crossref(new window)

17.
Arnaoutova I and Kleinman HK (2010) In vitro angiogenesis: endothelial cell tube formation on gelled basement membrane extract. Nat Protoc 5, 628-635 crossref(new window)

18.
Ghim J, Moon JS, Lee CS et al (2014) Endothelial deletion of phospholipase D2 reduces hypoxic response and pathological angiogenesis. Arterioscler Thromb Vasc Biol 34, 1697-1703 crossref(new window)

19.
Hedrich HJ and Bullock GR (2004) The laboratory mouse, Elsevier Academic Press, Amsterdam; Boston

20.
Aplin AC, Fogel E, Zorzi P and Nicosia RF (2008) The aortic ring model of angiogenesis. Methods Enzymol 443, 119-136 crossref(new window)

21.
Baker M, Robinson SD, Lechertier T et al (2012) Use of the mouse aortic ring assay to study angiogenesis. Nat Protoc 7, 89-104 crossref(new window)

22.
Dougher M and Terman BI (1999) Autophosphorylation of KDR in the kinase domain is required for maximal VEGF-stimulated kinase activity and receptor internalization. Oncogene 18, 1619-1627 crossref(new window)

23.
Takahashi T, Yamaguchi S, Chida K and Shibuya M (2001) A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J 20, 2768-2778 crossref(new window)

24.
Holmqvist K, Cross MJ, Rolny C et al (2004) The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular migration. J Biol Chem 279, 22267-22275 crossref(new window)

25.
Dayanir V, Meyer RD, Lashkari K and Rahimi N (2001) Identification of tyrosine residues in vascular endothelial growth factor receptor-2/FLK-1 involved in activation of phosphatidylinositol 3-kinase and cell proliferation. J Biol Chem 276, 17686-17692 crossref(new window)

26.
Fujio Y and Walsh K (1999) Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner. J Biol Chem 274, 16349-16354 crossref(new window)

27.
Warner AJ, Lopez-Dee J, Knight EL, Feramisco JR and Prigent SA (2000) The Shc-related adaptor protein, Sck, forms a complex with the vascular-endothelial-growthfactor receptor KDR in transfected cells. Biochem J 347, 501-509 crossref(new window)

28.
Takahashi T, Ueno H and Shibuya M (1999) VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene 18, 2221-2230 crossref(new window)

29.
Kroll J and Waltenberger J (1997) The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells. J Biol Chem 272, 32521-32527 crossref(new window)

30.
Matsumoto T, Bohman S, Dixelius J et al (2005) VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis. EMBO J 24, 2342-2353 crossref(new window)

31.
Zeng H, Sanyal S and Mukhopadhyay D (2001) Tyrosine residues 951 and 1059 of vascular endothelial growth factor receptor-2 (KDR) are essential for vascular permeability factor/vascular endothelial growth factor-induced endothelium migration and proliferation, respectively. J Biol Chem 276, 32714-32719 crossref(new window)

32.
Abedi H and Zachary I (1997) Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells. J Biol Chem 272, 15442-15451 crossref(new window)

33.
Fulton D, Gratton JP, McCabe TJ et al (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399, 597-601 crossref(new window)

34.
Schlaeppi JM and Wood JM (1999) Targeting vascular endothelial growth factor (VEGF) for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine-kinase inhibitors. Cancer Metastasis Rev 18, 473-481 crossref(new window)

35.
Carmeliet P, Ferreira V, Breier G et al (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380, 435-439 crossref(new window)

36.
Ferrara N, Carver-Moore K, Chen H et al (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380, 439-442 crossref(new window)

37.
Fong GH, Rossant J, Gertsenstein M and Breitman ML (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376, 66-70 crossref(new window)

38.
Shalaby F, Rossant J, Yamaguchi TP et al (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376, 62-66 crossref(new window)

39.
Dumont DJ, Jussila L, Taipale J et al (1998) Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science 282, 946-949 crossref(new window)

40.
Sugimoto H, Hamano Y, Charytan D et al (2003) Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem 278, 12605-12608 crossref(new window)

41.
Czarkowska-Paczek B, Bartlomiejczyk I and Przybylski J (2006) The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise. J Physiol Pharmacol 57, 189-197

42.
Takano S, Yoshii Y, Kondo S et al (1996) Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. Cancer Res 56, 2185-2190

43.
Kim GY, Park SY, Jo A et al (2015) Gecko proteins induce the apoptosis of bladder cancer 5637 cells by inhibiting Akt and activating the intrinsic caspase cascade. BMB Rep 48, 531-536 crossref(new window)

44.
Qin JF, Jin FJ, Li N et al (2015) Adrenergic receptor β2 activation by stress promotes breast cancer progression through macrophages M2 polarization in tumor microenvironment. BMB Rep 48, 295-300 crossref(new window)