Inhibition of WISE Preserves Renal Allograft Function

Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well u...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Society of Nephrology 2013-01, Vol.24 (1), p.66-76
Main Authors: XUEMING QIAN, XIAODONG YUAN, VALENTE, Eliane G, PRETORIUS, Jim, STENVENS, Jennitte L, TIPTON, Barbara, WINTERS, Aaron G, GRAHAM, Kevin, HARRISS, Lindsey, BAKER, Daniel M, DAMORE, Michael, SALIMI-MOOSAVI, Hossein, VONDERFECHT, Steven, YONGMING GAO, ELKHAL, Abdallah, PASZTY, Chris, SCOTT SIMONET, W, RICHARDS, William G, TULLIUS, Stefan G, XUPENG GE, LEE, Jae, JURISCH, Anke, LI ZHANG, YOU, Andrew, FITZPATRICK, Vincent D, WILLIAM, Alexia
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Antibodies - therapeutic use
Basic Research
beta Catenin - metabolism
Biological and medical sciences
Biomarkers - urine
Cadherins - metabolism
Carrier Proteins - antagonists & inhibitors
Carrier Proteins - metabolism
Epithelial Cells - metabolism
Fibroblasts - metabolism
Gene Expression
Humans
Kidney - immunology
Kidney - metabolism
Kidney Function Tests
Kidney Transplantation
Male
Medical sciences
Nephrology. Urinary tract diseases
Rats
Rats, Inbred F344
Rats, Inbred Lew
Renal Insufficiency - prevention & control
Renal Insufficiency - urine
Wnt Proteins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2012010012