Parallel microarray profiling identifies ErbB4 as a determinant of cyst growth in ADPKD and a prognostic biomarker for disease progression

Andrew J. Streets, Tajdida A. Magayr, Linghong Huang, Laura Vergoz, Sandro Rossetti, Roslyn J. Simms, Peter C Harris, Dorien J M Peters, Albert C M Ong

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common cause of endstage renal disease. The disease course can be highly variable and treatment options are limited. To identify new therapeutic targets and prognostic biomarkers of disease, we conducted parallel discovery microarray profiling in normal and diseased human PKD1 cystic kidney cells. A total of 1,515 genes and 5 miRNA were differentially expressed by more than twofold in PKD1 cells. Functional enrichment analysis identified 30 dysregulated signaling pathways including the epidermal growth factor (EGF) receptor pathway. In this paper, we report that the EGF/ErbB family receptor ErbB4 is a major factor driving cyst growth in ADPKD. Expression of ErbB4 in vivo was increased in human ADPKD and Pkd1 cystic kidneys, both transcriptionally and posttranscriptionally by mir-193b-3p. Ligand-induced activation of ErbB4 drives cystic proliferation and expansion suggesting a pathogenic role in cystogenesis. Our results implicate ErbB4 activation as functionally relevant in ADPKD, both as a marker of disease activity and as a new therapeutic target in this major kidney disease.

Original languageEnglish (US)
Pages (from-to)F577-F588
JournalAmerican Journal of Physiology - Renal Physiology
Volume312
Issue number4
DOIs
StatePublished - Apr 1 2017

Keywords

  • ADPKD
  • ErbB4 microRNA
  • Polycystin

ASJC Scopus subject areas

  • Physiology
  • Urology

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