Abstract
Aim:
To investigate the effects of CD151 on the activity of endothelial NO synthase (eNOS), and ECV304 migration, proliferation and tube formation.
Methods:
pAAV-CD151 and pAAV-anti-CD151 were constructed and used to transiently transfect ECV304 mediated with Lipofectamine 2000. After transfection, the expression of CD151 was measured by Western blotting. Cell migration assay was performed using Boyden transwell; proliferation assay was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5, diphenyltetrazoliumbromide (MTT) method, and tube formation test was examined on matrigel. eNOS activity was assayed by L-[3H]citrulline production from L-[3H]arginine. The involvement of eNOS was explored using an eNOS inhibitor (L-NAME) and the effects in the process were observed.
Results:
CD151 promotes cell migration, proliferation and tube formation. In addition, CD151 increases eNOS activity. Moreover, cell migration, proliferation and tube formation induced by CD151 are inhibited when L-NAME is used, which indicates that there is an involvement of eNOS in CD151-induced cell migration, cell proliferation and tube formation.
Conclusion:
CD151 promotes ECV304 migration, proliferation and tube formation. The mechanism is that CD151 increases eNOS activity. This result also suggests that eNOS is involved in the angiogenic effects of CD151.
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References
Stipp CS, Kolesnikova TV, Hemler ME . Functional domains in tetraspanin proteins. Trends Biochem Sci 2003; 28: 106–12.
Chometon G, Zhang ZG, Rubinstein E, Boucheix C, Mauch C, Aumailley M . Dissociation of the complex between CD151 and laminin-binding integrins permits migration of epithelial cells. Exp Cell Res 2006; 312: 983–95.
Zhang XA, Kazarov AR, Yang X, Bontrager AL, Stipp CS, Hemler ME . Function of the tetraspanin CD151-alpha6beta1 integrin complex during cellular morphogenesis. Mol Biol Cell 2002; 13: 1–11.
Lan RF, Liu ZX, Liu XC, Song YE, Wang DW . CD151 promotes neovascularization and improves blood perfusion in a rat hind-limb ischemia model. J Endovasc Ther 2005; 12: 469–78.
Lan RF, Liu ZX, Liu XC, Song YE, Wang DW . Effects of pAAV-CD151 and pAAV-antiCD151 on the migration of human tongue squamous carcinoma cell line Tca8113. J Huazhong Univ Sci Tech Med Sci 2004; 24: 556–9.
Zhao X, Lu X, Feng Q . Deficiency in endothelial nitric oxide synthase impairs myocardial angiogenesis. Am J Physiol Heart Circ Physiol 2002; 283: H2371–78.
Morbidelli L, Donnini S, Ziche M . Role of nitric oxide in tumor angiogenesis. Cancer Treat Res 2004; 117: 155–67.
Isenberg JS . Nitric oxide modulation of early angiogenesis. Microsurgery 2004; 24: 385–91.
Yauch RL, Berditchevski F, Harler MB, Reichner J, Hemler ME . Highly stoichiometric, stable, and specific association of integrin α3β1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration. Mol Biol Cell 1998; 9: 2751–65.
Yanez-Mo M, Alfranca A, Cabañas C, Marazuela M, Tejedor R, Ursa MA, et al. Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with α3β1 integrin localized at endothelial lateral junctions. J Cell Biol 1998; 141: 791–804.
Dimmeler, S, Dernbach E, Zeiher AM . Phosphorylation of the endothelial nitric oxide synthase at Ser-1177 is required for VEGF-induced endothelial cell migration. FEBS Lett 2000; 477: 258–62.
Gooch KJ, Dangler CA, Frangos JA . Exogenous, basal, and flow-induced nitric oxide production and endothelial cell proliferation. J Cell Physiol 1997; 171: 252–8.
Murohara T, Asahara T, Silver M, Bauters C, Masuda H, Kalka C, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Investig 1998; 101: 2567–78.
Zhang XA, Bontrager AL, Hemler ME . Transmembrane-4 superfamily proteins associate with activated protein kinase C (PKC) and link PKC to specific beta (1) integrins. J Biol Chem 2001; 276: 25005–13.
Berditchevski F, Gilbert E, Griffiths MR, Fitter S, Ashman L, Jenner SL . Analysis of the CD151- alpha3beta1 integrin and CD151-tetraspanin interactions by mutagenesis. J Biol Chem 2001; 276: 41165–74.
Partovian C, Zhuang Z, Moodie K, Lin M, Ouchi N, Sessa WC, et al. PKCalpha activates eNOS and increases arterial blood flow in vivo. Circ Res 2005; 97: 482–7.
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Project supported by a grant from the National Natural Science Foundation of China (No 30570728) and the Science Research Foundation of the Health Department of Hubei Province (No JX2A04).
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Zheng, Zz., Liu, Zx. CD151 gene delivery increases eNOS activity and induces ECV304 migration, proliferation and tube formation. Acta Pharmacol Sin 28, 66–72 (2007). https://doi.org/10.1111/j.1745-7254.2007.00490.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00490.x
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