gms | German Medical Science

125. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

22. - 25.04.2008, Berlin

GBP-1 inhibits spreading and migration of endothelial cells on fibronectin through induction of integrin alpha4 expression

Meeting Abstract

  • corresponding author K. Weinländer - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg
  • E. Naschberger - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg
  • M. Lehmann - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg
  • W. Hohenberger - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg
  • M. Stürzl - Division of Molecular and Experimental Surgery, Departement of Surgery, University of Erlangen-Nuremberg

Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. Doc08dgch9104

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgch2008/08dgch320.shtml

Veröffentlicht: 16. April 2008

© 2008 Weinländer et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Human guanylate binding protein-1 (GBP-1) is a large secreted [1] GTPase, which exerts potent anti-angiogenic activities in endothelial cells (EC) [2], [3]. To date, the molecular mechanisms of these anti-angiogenic activities of GBP-1 have not been elucidated.

Materials and methods: Comparative transcriptome analysis were performed with human umbilical vein endothelial cells (HUVEC) stably expressing GBP-1 and control cells using HG-U133 Plus 2.0 GenChip (Affymetrix). Results were confirmed at RNA level by RNase protection assay and at protein level by FACS analysis using a monoclonal antibody against ITGA4. Specific knock-down of GBP-1 was done using vector based RNAi technology (shRNA vector systems). Cell spreading and migratory behaviour (wound healing assay) of the HUVEC was studied on fibronectin coated plates.

Results: Comparative transcriptome analysis of HUVEC showed that GBP-1 induces expression of integrin alpha4 (ITGA4), both at mRNA and protein level. In addition, treatment of HUVEC with interleukin (IL)-1β and tumor necrosis factor (TNF)-α, both activators of endogenous GBP-1 expression, induced ITGA4 expression, whereas specific knock-down of GBP-1 in these cells abrogated ITGA4 expression. These findings indicated that GBP-1 expression was both, necessary and sufficient for the induction of ITGA4 expression by IL-1β and TNF-α. Further cell biological characterization showed that increased ITGA4 expression inhibited cell spreading and migration of HUVEC on fibronectin and that both features could be restored by inhibition of GBP-1 expression.

Conclusion: Cell spreading and migration are key events during angiogenesis. The inhibition of cell spreading and migration through up-regulation of ITGA4 provides a novel mechanism to explain the anti-invasive activity of GBP-1 in endothelial cells.


References

1.
Naschberger et al. Am J Pathol. 2006.
2.
Guenzi et al. EMBO J. 2003.
3.
Guenzi et al. EMBO J. 2001.