Increased expression of secreted frizzled-related protein 4 in polycystic kidneys

Daniel Romaker, Michael Puetz, Sven Teschner, Johannes Donauer, Marcel Geyer, Peter Gerke, Brigitta Rumberger, Bernd Dworniczak, Petra Pennekamp, Björn Buchholz, H. P.H. Neumann, Rajiv Kumar, Joachim Gloy, Kai Uwe Eckardt, Gerd Walz

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease associated with progressive renal failure. Although cyst growth and compression of surrounding tissue may account for some loss of renal tissue, the other factors contributing to the progressive renal failure in patients with ADPKD are incompletely understood. Here, we report that secreted frizzled-related protein 4 (sFRP4) is upregulated in human ADPKD and in four different animal models of PKD, suggesting that sFRP4 expression is triggered by a common mechanism that underlies cyst formation. Cyst fluid from ADPKD kidneys activated the sFRP4 promoter and induced production of sFRP4 protein in renal tubular epithelial cell lines. Antagonism of the vasopressin 2 receptor blocked both promoter activity and tubular sFRP4 expression. In addition, sFRP4 selectively influenced members of the canonical Wnt signaling cascade and promoted cystogenesis of the zebrafish pronephros. sFRP4 was detected in the urine of both patients and animals with PKD, suggesting that sFRP4 may be a potential biomarker for monitoring the progression of ADPKD. Taken together, these observations suggest a potential role for SFRP4 in the pathogenesis of ADPKD.

Original languageEnglish (US)
Pages (from-to)48-56
Number of pages9
JournalJournal of the American Society of Nephrology
Volume20
Issue number1
DOIs
StatePublished - Jan 2009

ASJC Scopus subject areas

  • Nephrology

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    Romaker, D., Puetz, M., Teschner, S., Donauer, J., Geyer, M., Gerke, P., Rumberger, B., Dworniczak, B., Pennekamp, P., Buchholz, B., Neumann, H. P. H., Kumar, R., Gloy, J., Eckardt, K. U., & Walz, G. (2009). Increased expression of secreted frizzled-related protein 4 in polycystic kidneys. Journal of the American Society of Nephrology, 20(1), 48-56. https://doi.org/10.1681/ASN.2008040345