Skip to main content
SpringerLink
Log in

Vascular endothelial growth factor upregulates follistatin in human umbilical vein endothelial cells

  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

Vascular endothelial growth factor (VEGF), plays a key role in angiogenesis. Many endogenous factors can affect angiogenesis in endothelial cells. VEGF is known to be a strong migration, sprouting, survival, and proliferation factor for endothelial cells during angiogenesis in endothelial cells. Searching for novel genes, involved in VEGF signaling during angiogenesis, we carried out differential display polymerase chain reaction on RNA from VEGF-stimulated human umbilical vein endothelial cells (HUVECs). In this study, follistatin (FS) differentially expressed in VEGF-treated HUVECs, compared with controls. Addition of VEGF (10 ng/mL) produced an approximately 11.8-fold increase of FS mRNA. FS or VEGF produced approximately 1.8- or 2.9-fold increases, respectively, in matrix metalloproteinase-2 (MMP-2) secretion for 12 h, compared to the addition of a control buffer. We suggest that VEGF may affect the angiogenic effect of HUVECs, through a combination of the direct effects of VEGF itself, and the indirect effects mediated via induction of FSin vitro.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gerber, H. P., A. McMurtrey, J. Kowalski, M. Yan, B. A. Keyt, V. Dixit, and N. Ferrara (1998) Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway.J. Biol. Chem. 273: 30336–30343.

    Article  CAS  Google Scholar 

  2. Ferrara, N. (1996) Vascular endothelial growth factor.Eur. J. Cancer 32: 2413–2422.

    Article  Google Scholar 

  3. Carmeliet, P. (2003) Angiogenesis in health and disease.Nat. Med. 9: 653–660.

    Article  CAS  Google Scholar 

  4. de Vries, C., J. A. Escobedo, H. Ueno, K. Houck, N. Ferrara, and L. T. Williams (1992) The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor.Science 255: 989–991.

    Article  Google Scholar 

  5. Millauer, B., S. Wizigmann-Voos, H. Schnurch, R. Martinez, N. P. H. Moller, W. Risau, and A. Ulrich (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis.Cell 72: 835–846.

    Article  CAS  Google Scholar 

  6. Hockel, M., K. Schlenger, S. Doctrow, T. Kissel, and P. Vaupel (1993) Therapeutic angiogenesis.Arch. Surg. 128: 423–429.

    CAS  Google Scholar 

  7. Isner, J. M. and D. W. Losordo (2003) Therapeutic angiogenesis for heart failure.Nat. Med. 5: 491–492.

    Article  Google Scholar 

  8. Brusselmans, K., F. Bono, P. Maxwell, Y. Dor, M. Dewerchin, D. Collen, J. M. Herbert, and P. Carmeliet (2001) Hypoxia-inducible factor-2alpha (HIF-2alpha) is involved in the apoptotic response to hypoglycemia but not to hypoxia.J. Biol. Chem. 276: 39192–39196.

    Article  CAS  Google Scholar 

  9. Neufeld, G., T. Cohen, S. Gengrinovitch, and Z. Poltorak (1999) Vascular endothelial growth factor (VEGF) and its receptors.FASEB J. 13: 9–22.

    CAS  Google Scholar 

  10. Robertson, D. M., R. Klein, F. L. de Vos, R. I. McLachlan, R. E. Wettenhall, M. T. Hearn, H. G. Burger, and D. M. de Kretser (1987) The isolation of polypeptides with FSH suppressing activity from bovine follicular fluid which are structurally different to inhibin.Biochem. Biophys. Res. Commu. 149: 744–749.

    Article  CAS  Google Scholar 

  11. Ueno, N., N. Ling, S. Y. Ying, F. Esch, S. Shimasaki, and R. Guillemin (1987) Isolation and partial characterization of follistatin: a single-chain Mr 35,000 monomeric protein that inhibits the release of follicle-stimulating hormone.Proc. Natl. Acad. Sci. USA 84: 8282–8286.

    Article  CAS  Google Scholar 

  12. Kawakami, S., Y. Fujii, and S. J. Winters (2001) Follistatin production by skin fibroblasts and its regulation by dexamethasone.Mol. Cell. Endocrinol. 172: 157–167.

    Article  CAS  Google Scholar 

  13. DePaolo, L. V. (1997) Inhibins, activins, and follistatins: the saga continues.Exp. Biol. Med. 214: 328–339.

    CAS  Google Scholar 

  14. Risau, W. (1997) Mechanisms of angiogenesis.Nature 386: 671–674.

    Article  CAS  Google Scholar 

  15. Folkman, J. and Y. Shing (1992) Angiogenesis.J. Biol. Chem. 267: 10931–10934.

    CAS  Google Scholar 

  16. Brooks, P. C., S. Silletti, T. L. von Schalscha, M. Friedlander, and D. A. Cheresh (1998) Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity.Cell 92: 391–400.

    Article  CAS  Google Scholar 

  17. Liang, P. and A. B. Pardee (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction.Science 257: 967–971.

    Article  CAS  Google Scholar 

  18. Kim, I., S. O. Moon, K. N. Koh, H. Kim, C. S. Uhm, H. J. Kwak, N. G. Kim, and G.Y. Koh (1999) Molecular cloning, expression, and characterization of angiopoietin-related protein induces endothelial cell sprouting.J. Biol. Chem. 274: 26523–26528.

    Article  CAS  Google Scholar 

  19. Kleinen, D. E., I. M. K. Margulis, W. G. Stetler-Stevenson (1998) Cell and tissue culture: Laboratory procedures. pp. 5A7.1–5A7.8. In: A. Doyle, J. B. Griffiths, and D. G. Newell (eds.), Wiley, Sussex, UK.

    Google Scholar 

  20. Badruddoja, M. A., H. G. Krouwer, S. D. Rand, K.J. Rebro, A. P. Pathak, and K. M. Schmainda (2003) Antiangiogenic effects of dexamethasone in 9L gliosarcoma assessed by MRI cerebral blood volume maps.Neuro-oncol. 5: 235–243.

    Article  CAS  Google Scholar 

  21. Clerch, L. B., A. S. Baras, G. D. Massaro, E. P. Hoffman, and D. Massaro (2004) DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation.Am. J. Physiol. Lung Cell. Mol. Physiol. 286: 411–419.

    Article  Google Scholar 

  22. Kaiser, U. B., B. L. Lee, R. S. Carroll, G. Unabia, W. W. Chin, and G. V. Childs (1992) Follistatin gene expression in the pituitary: localization in gonadotropes and folliculostellate cells in diestrous rats.Endocrinology 130: 3048–3056.

    Article  CAS  Google Scholar 

  23. Kozian, D. H., M. Ziche, and H. G. Augustin (1997) The activin-binding protein follistatin regulates autocrine endothelial cell activity and induces angiogenesis.Lab. Invest. 76: 267–276.

    CAS  Google Scholar 

  24. Pepper, J. S., R. Montesano, S. J. Mandriota, L. Orci, and J. D. Vassalli (1996) Angiogenesis: a paradigm for balanced extracellular proteolysis during cell migration and morphogenesis.Enzyme Protein 49: 138–162.

    CAS  Google Scholar 

  25. Hiraoka, N., E. Allen, I. J. Apel, M. R. Gyetko, and S. J. Weiss (1998) Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins.Cell 95: 365–377.

    Article  CAS  Google Scholar 

  26. Brown, M. D. and O. Hudlicka (2003) Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: involvement of VEGF and metalloproteinases.Angiogenesis 6: 1–14.

    Article  CAS  Google Scholar 

  27. Kliche, S. and J. Waltenberger (2001) VEGF receptor signaling and endothelial function.IUBMB Life 52: 61–66.

    Article  CAS  Google Scholar 

  28. Wang, H. and J. A. Keiser (1998) Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1.Circ. Res. 83: 832–840.

    CAS  Google Scholar 

  29. Itaya, H., T. Imaizumi, H. Yoshida, M. Koyama, S. Suzuki, and K. Satoh (2001) Expression of vascular endothelial growth factor in human monocyte/macrophages stimulated with lipopolysaccharide.Thromb. Haemost. 85: 171–176.

    CAS  Google Scholar 

  30. Haas, T. L., M. Milkiewicz, S. J. Davis, A. L. Zhou, S. Egginton, M. D. Brown, J. A. Madri, and O. Hudlicka (2000) Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle.Am. J. Physiol. Heart Circ. Physiol. 279: 1540–1547.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Biological Sciences, Institute for Molecular Biology & Genetics, Chonbuk National University, Chonju, 561-756, Chonbuk, Korea

    In Suk Oh & Hwan Gyu Kim

Authors
  1. In Suk Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hwan Gyu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hwan Gyu Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, I.S., Kim, H.G. Vascular endothelial growth factor upregulates follistatin in human umbilical vein endothelial cells. Biotechnol. Bioprocess Eng. 9, 201–206 (2004). https://doi.org/10.1007/BF02942293

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02942293

Keywords

Search

Navigation