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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-20253

von Toerne, C; Schmidt, C; Adams, J; Kiss, E; Bedke, J; Porubsky, S; Gretz, N; Lindenmeyer, M T; Cohen, C D; Gröne, H J; Nelson, P J (2009). Wnt pathway regulation in chronic renal allograft damage. American Journal of Transplantation, 9(10):2223-2239.

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The Wnt signaling pathway, linked to development, has been proposed to be recapitulated during the progressive damage associated with chronic organ failure. Chronic allograft damage following kidney transplantation is characterized by progressive fibrosis and a smoldering inflammatory infiltrate. A modified, Fischer 344 (RT1(lvl)) to Lewis (RT1(l)) rat renal allograft model that reiterates many of the major pathophysiologic processes seen in patients with chronic allograft failure was used to study the progressive disease phenotype and specific gene product expression by immunohistochemistry and transcriptomic profiling. Central components of the Tgfb, canonical Wnt and Wnt-Ca2+ signaling pathways were significantly altered with the development of chronic damage. In the canonical Wnt pathway, Wnt3, Lef1 and Tcf1 showed differential regulation. Target genes Fn1, Cd44, Mmp7 and Nos2 were upregulated and associated with the progression of renal damage. Changes in the Wnt-Ca2+ pathway were evidenced by increased expression of Wnt6, Wnt7a, protein kinase C, Cam Kinase II and Nfat transcription factors and the target gene vimentin. No evidence for alterations in the Wnt planar cell polarity (PCP) pathway was detected. Overall results suggest cross talk between the Wnt and Tgfb signaling pathways during allograft inflammatory damage and present potential targets for therapeutic intervention.


37 citations in Web of Science®
39 citations in Scopus®
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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:22 July 2009
Deposited On:18 Aug 2009 11:42
Last Modified:05 Apr 2016 13:19
Publisher DOI:10.1111/j.1600-6143.2009.02762.x
PubMed ID:19681821

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