2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2006091012v1 18/6/1697    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wilkinson, L. Articles by Little, M. H. Search for Related Content PubMed PubMed Citation Articles by Wilkinson, L. Articles by Little, M. H.

Crim1^{KST264/KST264} Mice Implicate Crim1 in the Regulation of Vascular Endothelial Growth Factor-A Activity during Glomerular Vascular Development

Lorine Wilkinson^*, Thierry Gilbert^*, Genevieve Kinna^*, Leah-Anne Ruta, David Pennisi^*, Michelle Kett and Melissa H. Little^*

^* Institute for Molecular Bioscience, University of Queensland, Brisbane, and Department of Physiology, Monash University, Melbourne, Australia

Address correspondence to: Prof. Melissa H. Little, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia 4072. Phone: +61-7-3346-2054; Fax: +61-7-3346-2101; E-mail: m.little{at}imb.uq.edu.au

Received for publication September 15, 2006. Accepted for publication March 15, 2007.

Crim1, a transmembrane cysteine-rich repeat–containing protein that is related to chordin, plays a role in the tethering of growth factors at the cell surface. Crim1 is expressed in the developing kidney; in parietal cells, podocytes, and mesangial cells of the glomerulus; and in pericytes that surround the arterial vasculature. A gene-trap mouse line with an insertion in the Crim1 gene (Crim1^{KST264/KST264}) displayed perinatal lethality with defects in multiple organ systems. This study further analyzed the defects that are present within the kidneys of these mice. Crim1^{KST264/KST264} mice displayed abnormal glomerular development, illustrated by enlarged capillary loops, podocyte effacement, and mesangiolysis. When outbred, homozygotes that reached birth displayed podocyte and glomerular endothelial cell defects and marked albuminuria. The podocytic co-expression of Crim1 with vascular endothelial growth factor-A (VEGF-A) suggested a role for Crim1 in the regulation of VEGF-A action. Crim1 and VEGF-A were shown to interact directly, providing evidence that cysteine-rich repeat–containing proteins can bind to non–TGF- superfamily ligands. Crim1^{KST264/KST264} mice display a mislocalization of VEGF-A within the developing glomerulus, as assessed by immunogold electron microscopy and increased activation of VEGF receptor 2 (Flk1) in the glomerular endothelial cells, suggesting that Crim1 regulates the delivery of VEGF-A by the podocytes to the endothelial cells. This is the first in vivo demonstration of regulation of VEGF-A delivery and supports the hypothesis that Crim1 functions to regulate the release of growth factors from the cell of synthesis.

This article has been cited by other articles:

				E. Bjorling, C. Lindskog, P. Oksvold, J. Linne, C. Kampf, S. Hober, M. Uhlen, and F. Ponten A Web-based Tool for in Silico Biomarker Discovery Based on Tissue-specific Protein Profiles in Normal and Cancer Tissues Mol. Cell. Proteomics, May 1, 2008; 7(5): 825 - 844. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673