Skip Navigation



NDT Advance Access published online on May 9, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp182
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
24/9/2637    most recent
gfp182v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by van den Hoven, M. J.
Right arrow Articles by van der Vlag, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van den Hoven, M. J.
Right arrow Articles by van der Vlag, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Regulation of glomerular heparanase expression by aldosterone, angiotensin II and reactive oxygen species

Mabel J. van den Hoven1,*, Femke Waanders2,3*, Angelique L. Rops1,*, Andrea B. Kramer2,3, Harry van Goor3, Jo H. Berden1, Gerjan Navis2 and Johan van der Vlag1

1 Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen 2 Department of Nephrology 3 Department of Pathology and Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

Correspondence and offprint requests to: Johan van der Vlag; E-mail: J.vanderVlag{at}nier.umcn.nl



  Abstract

Background. Inhibition of the renin–angiotensin–aldosterone system (RAAS) provides renoprotection in adriamycin nephropathy (AN), along with a decrease in overexpression of glomerular heparanase. Angiotensin II (AngII) and reactive oxygen species (ROS) are known to regulate heparanase expression in vivo. However, it is unknown whether this is also the case for aldosterone. Therefore, we further assessed the role of aldosterone, AngII and ROS in the regulation of glomerular heparanase expression.

Methods. Six weeks after the induction of AN, rats were treated with vehicle (n = 8), lisinopril (75 mg/L, n = 10), spironolactone (3.3 mg/day, n = 12) or the combination of lisinopril and spironolactone (n = 14) for 12 weeks. Age-matched healthy rats served as controls (n = 6). After 18 weeks, renal heparanase and heparan sulfate (HS) expression were examined by immunofluorescence staining. In addition, the effect of aldosterone, AngII and ROS on heparanase expression in cultured podocytes was determined.

Results. Treatment with lisinopril, spironolactone or their combination significantly blunted the increased glomerular heparanase expression and restored the decreased HS expression in the GBM. Addition of aldosterone to cultured podocytes resulted in a significantly increased heparanase mRNA and protein expression, which could be inhibited by spironolactone. Heparanase mRNA and protein expression in podocytes were also significantly increased after stimulation with AngII or ROS.

Conclusions. Our in vivo and in vitro results show that not only AngII and ROS, but also aldosterone is involved in the regulation of glomerular heparanase expression.

Keywords: glomerular basement membrane; heparan sulfate; heparanase; proteinuria; renin–angiotensin–aldosterone system

* Contributed equally.

Received for publication: 20. 5.07
Accepted in revised form: 30. 3.09


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.