JCB logo
CrossRef
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 747K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Esser, S.
Right arrow Articles by Risau, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Esser, S.
Right arrow Articles by Risau, W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/1998//947 $5.00
The Journal of Cell Biology, Volume 140, Number 4, , 1998 947-959

Article

Vascular Endothelial Growth Factor Induces Endothelial Fenestrations In Vitro



Sybille Esser*, Karen Wolburg{ddagger}, Hartwig Wolburg{ddagger}, Georg Breier*, Teymuras Kurzchalia§, and Werner Risau*

* Max Planck Institut für Physiologische und Klinische Forschung, W.G. Kerckhoff Institut, Abteilung Molekulare Zellbiologie, D-61231 Bad Nauheim; {ddagger} Institut für Pathologie, Universität Tübingen, D-72076 Tübingen; and § Max Delbrück Centrum für Molekulare Medizin, D-13122 Berlin, Germany

Abstract. Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis, angiogenesis, and vascular permeability. In contrast to its transient expression during the formation of new blood vessels, VEGF and its receptors are continuously and highly expressed in some adult tissues, such as the kidney glomerulus and choroid plexus. This suggests that VEGF produced by the epithelial cells of these tissues might be involved in the induction or maintenance of fenestrations in adjacent endothelial cells expressing the VEGF receptors. Here we describe a defined in vitro culture system where fenestrae formation was induced in adrenal cortex capillary endothelial cells by VEGF, but not by fibroblast growth factor. A strong induction of endothelial fenestrations was observed in cocultures of endothelial cells with choroid plexus epithelial cells, or mammary epithelial cells stably transfected with cDNAs for VEGF 120 or 164, but not with untransfected cells. These results demonstrate that, in these cocultures, VEGF is sufficient to induce fenestrations in vitro. Identical results were achieved when the epithelial cells were replaced by an epithelial-derived basal lamina-type extracellular matrix, but not with collagen alone. In this defined system, VEGF-mediated induction of fenestrae was always accompanied by an increase in the number of fused diaphragmed caveolae-like vesicles. Caveolae, but not fenestrae, were labeled with a caveolin-1–specific antibody both in vivo and in vitro. VEGF stimulation led to VEGF receptor tyrosine phosphorylation, but no change in the distribution, phosphorylation, or protein level of caveolin-1 was observed. We conclude that VEGF in the presence of a basal lamina-type extracellular matrix specifically induces fenestrations in endothelial cells. This defined in vitro system will allow further study of the signaling mechanisms involved in fenestrae formation, modification of caveolae, and vascular permeability.

We thank B. Engelhardt, H. Drexler, S. Bamforth (all from Max Planck Institut für physiologische und klinische Forschung), U. Kniesel, and H. Gerhardt (Universität Tübingen) for their helpful comments on the manuscript.

This work was supported by the Max Planck Society and SUGEN, Inc.

Address all correspondence to Werner Risau, Max Planck Institut für Physiologische und Klinische Forschung, W.G. Kerckhoff Institut, Abteilung Molekulare Zellbiologie, Parkstr. 1, 61231 Bad Nauheim, Germany. Tel.: (49) 603-272-073. Fax: (49) 603-272-259. E-mail: wrisau{at}kerckhoff.mpg.de

1. Abbreviations used in this paper: ACE, adrenal cortex endothelial cells; CPE, choroid plexus epithelial cells; HMSS, Hanks modified salt solution; HUVEC, human umbilical vein endothelial cells; PMA, phorbol myristate acetate; RT, reverse transcription; VEGF, vascular endothelial growth factor; VVO, vesiculo-vacuolar organelle.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents