This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Viñals, F.
Right arrow Articles by Pouysségur, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Viñals, F.
Right arrow Articles by Pouysségur, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2001, p. 7218-7230, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7218-7230.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Transforming Growth Factor beta 1 (TGF-beta 1) Promotes Endothelial Cell Survival during In Vitro Angiogenesis via an Autocrine Mechanism Implicating TGF-alpha Signaling

Francesc Viñals* and Jacques Pouysségur*

Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543-Centre Antoine Lacassagne, 06189 Nice Cedex 2, France

Received 2 March 2001/Returned for modification 19 April 2001/Accepted 6 August 2001

Mouse capillary endothelial cells (1G11 cell line) embedded in type I collagen gels undergo in vitro angiogenesis. Cells rapidly reorganize and form capillary-like structures when stimulated with serum. Transforming growth factor beta 1 (TGF-beta 1) alone can substitute for serum and induce cell survival and tubular network formation. This TGF-beta 1-mediated angiogenic activity depends on phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase (MAPK) signaling. We showed that specific inhibitors of either pathway (wortmannin, LY-294002, and PD-98059) all suppressed TGF-beta 1-induced angiogenesis mainly by compromising cell survival. We established that TGF-beta 1 stimulated the expression of TGF-alpha mRNA and protein, the tyrosine phosphorylation of a 170-kDa membrane protein representing the epidermal growth factor (EGF) receptor, and the delayed activation of PI3K/Akt and p42/p44 MAPK. Moreover, we showed that all these TGF-beta 1-mediated signaling events, including tubular network formation, were suppressed by incubating TGF-beta 1-stimulated endothelial cells with a soluble form of an EGF receptor (ErbB-1) or tyrphostin AG1478, a specific blocker of EGF receptor tyrosine kinase. Finally, addition of TGF-alpha alone poorly stimulated angiogenesis; however, by reducing cell death, it strongly potentiated the action of TGF-beta 1. We therefore propose that TGF-beta 1 promotes angiogenesis at least in part via the autocrine secretion of TGF-alpha , a cell survival growth factor, activating PI3K/Akt and p42/p44 MAPK.

* Corresponding author. Present address for Francese Viñals: Facultad de Odontologia, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. E-mail: fvinals{at}bell.ub.es. Mailing address for Jacques Pouysségur: Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543-Centre Antoine Lacassagne, 33 Av. Valombrose, 06189 Nice Cedex 2, France. Phone: (33) 492 03 1222. Fax: (33) 492 03 1225. E-mail: pouysseg{at}unice.fr.

Molecular and Cellular Biology, November 2001, p. 7218-7230, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7218-7230.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lu, Q., Patel, B., Harrington, E. O., Rounds, S. (2009). Transforming growth factor-{beta}1 causes pulmonary microvascular endothelial cell apoptosis via ALK5. Am. J. Physiol. Lung Cell. Mol. Physiol. 296: L825-L838 [Abstract] [Full Text]  
  • Sawada, N., Kim, H.-H., Moskowitz, M. A., Liao, J. K. (2009). Rac1 Is a Critical Mediator of Endothelium-Derived Neurotrophic Activity. Sci Signal 2: ra10-ra10 [Abstract] [Full Text]  
  • Ismail, S., Sturrock, A., Wu, P., Cahill, B., Norman, K., Huecksteadt, T., Sanders, K., Kennedy, T., Hoidal, J. (2009). NOX4 mediates hypoxia-induced proliferation of human pulmonary artery smooth muscle cells: the role of autocrine production of transforming growth factor-{beta}1 and insulin-like growth factor binding protein-3. Am. J. Physiol. Lung Cell. Mol. Physiol. 296: L489-L499 [Abstract] [Full Text]  
  • Belladonna, M. L., Volpi, C., Bianchi, R., Vacca, C., Orabona, C., Pallotta, M. T., Boon, L., Gizzi, S., Fioretti, M. C., Grohmann, U., Puccetti, P. (2008). Cutting Edge: Autocrine TGF-{beta} Sustains Default Tolerogenesis by IDO-Competent Dendritic Cells. J. Immunol. 181: 5194-5198 [Abstract] [Full Text]  
  • Wang, S. E., Xiang, B., Guix, M., Olivares, M. G., Parker, J., Chung, C. H., Pandiella, A., Arteaga, C. L. (2008). Transforming Growth Factor {beta} Engages TACE and ErbB3 To Activate Phosphatidylinositol-3 Kinase/Akt in ErbB2-Overexpressing Breast Cancer and Desensitizes Cells to Trastuzumab. Mol. Cell. Biol. 28: 5605-5620 [Abstract] [Full Text]  
  • Airoldi, I., Cocco, C., Giuliani, N., Ferrarini, M., Colla, S., Ognio, E., Taverniti, G., Di Carlo, E., Cutrona, G., Perfetti, V., Rizzoli, V., Ribatti, D., Pistoia, V. (2008). Constitutive expression of IL-12R{beta}2 on human multiple myeloma cells delineates a novel therapeutic target. Blood 112: 750-759 [Abstract] [Full Text]  
  • Lu, Q. (2008). Transforming growth factor-{beta}1 protects against pulmonary artery endothelial cell apoptosis via ALK5. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L123-L133 [Abstract] [Full Text]  
  • Tran, T. C., Sneed, B., Haider, J., Blavo, D., White, A., Aiyejorun, T., Baranowski, T. C., Rubinstein, A. L., Doan, T. N., Dingledine, R., Sandberg, E. M. (2007). Automated, Quantitative Screening Assay for Antiangiogenic Compounds Using Transgenic Zebrafish. Cancer Res. 67: 11386-11392 [Abstract] [Full Text]  
  • Levashova, Z. B., Sharma, N., Timofeeva, O. A., Dome, J. S., Perantoni, A. O. (2007). ELR+-CXC Chemokines and Their Receptors in Early Metanephric Development. J. Am. Soc. Nephrol. 18: 2359-2370 [Abstract] [Full Text]  
  • Kutcher, M. E., Kolyada, A. Y., Surks, H. K., Herman, I. M. (2007). Pericyte Rho GTPase Mediates Both Pericyte Contractile Phenotype and Capillary Endothelial Growth State. Am. J. Pathol. 171: 693-701 [Abstract] [Full Text]  
  • Castanares, C., Redondo-Horcajo, M., Magan-Marchal, N., ten Dijke, P., Lamas, S., Rodriguez-Pascual, F. (2007). Signaling by ALK5 mediates TGF-beta-induced ET-1 expression in endothelial cells: a role for migration and proliferation. J. Cell Sci. 120: 1256-1266 [Abstract] [Full Text]  
  • Lebrin, F., Deckers, M., Bertolino, P., ten Dijke, P. (2005). TGF-{beta} receptor function in the endothelium. Cardiovasc Res 65: 599-608 [Abstract] [Full Text]  
  • Kim, S. J., Uehara, H., Yazici, S., Langley, R. R., He, J., Tsan, R., Fan, D., Killion, J. J., Fidler, I. J. (2004). Simultaneous Blockade of Platelet-Derived Growth Factor-Receptor and Epidermal Growth Factor-Receptor Signaling and Systemic Administration of Paclitaxel as Therapy for Human Prostate Cancer Metastasis in Bone of Nude Mice. Cancer Res. 64: 4201-4208 [Abstract] [Full Text]  
  • Chung, C.-H., Wu, W.-B., Huang, T.-F. (2004). Aggretin, a snake venom-derived endothelial integrin {alpha}2{beta}1 agonist, induces angiogenesis via expression of vascular endothelial growth factor. Blood 103: 2105-2113 [Abstract] [Full Text]  
  • Shih, S.-C., Ju, M., Liu, N., Mo, J.-R., Ney, J. J., Smith, L. E. H. (2003). Transforming growth factor {beta}1 induction of vascular endothelial growth factor receptor 1: Mechanism of pericyte-induced vascular survival in vivo. Proc. Natl. Acad. Sci. USA 100: 15859-15864 [Abstract] [Full Text]  
  • Dupont, J., McNeilly, J., Vaiman, A., Canepa, S., Combarnous, Y., Taragnat, C. (2003). Activin Signaling Pathways in Ovine Pituitary and L{beta}T2 Gonadotrope Cells. Biol. Reprod. 68: 1877-1887 [Abstract] [Full Text]  
  • Subramaniam, S., Strelau, J., Unsicker, K. (2003). Growth Differentiation Factor-15 Prevents Low Potassium-induced Cell Death of Cerebellar Granule Neurons by Differential Regulation of Akt and ERK Pathways. J. Biol. Chem. 278: 8904-8912 [Abstract] [Full Text]  
  • Bhagwat, S. V., Petrovic, N., Okamoto, Y., Shapiro, L. H. (2003). The angiogenic regulator CD13/APN is a transcriptional target of Ras signaling pathways in endothelial morphogenesis. Blood 101: 1818-1826 [Abstract] [Full Text]  
  • RODRIGUES, S., VAN AKEN, E., VAN BOCXLAER, S., ATTOUB, S., NGUYEN, Q.-D., BRUYNEEL, E., WESTLEY, B. R., MAY, F. E. B., THIM, L., MAREEL, M., GESPACH, C., EMAMI, S. (2003). Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cyclooxygenase-2 and EGF receptor signaling. FASEB J. 17: 7-16 [Abstract] [Full Text]  
  • Ghosh-Choudhury, N., Abboud, S. L., Nishimura, R., Celeste, A., Mahimainathan, L., Choudhury, G. G. (2002). Requirement of BMP-2-induced Phosphatidylinositol 3-Kinase and Akt Serine/Threonine Kinase in Osteoblast Differentiation and Smad-dependent BMP-2 Gene Transcription. J. Biol. Chem. 277: 33361-33368 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»