MicroRNAs regulate renal tubule maturation through modulation of Pkd1

Vishal Patel, Sachin Hajarnis, Darren Williams, Ryan Hunter, Donovan Huynh, Peter Igarashi

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

MicroRNAs (miRNAs) contribute to the regulation of early kidney development, but their role during later stages of renal tubulematuration is not well understood. Here, we found that ablation of the miRNA-processing enzyme Dicer from maturing renal tubules produces tubular and glomerular cysts in mice. Inactivation of Dicer is associated with downregulation of miR-200, a kidney-enriched miRNA family, and upregulation of the polycystic kidney disease gene Pkd1. Inhibition of miR-200 in cultured renal epithelial cells disrupted tubulogenesis and led to upregulation of Pkd1. Using bioinformatic and in vitro approaches, we found that miR-200b/c/429 induce post-transcriptional repression of Pkd1 through two conserved binding sites in the 39-Untranslated regions of Pkd1. Overexpression of PKD1 in renal epithelial cells was sufficient to disrupt tubulogenesis and produce cyst-like structures. In conclusion, miRNAs are essential for the maturation of renal tubules, and Pkd1 is a target of miR-200. These results also suggest that miRNAs may modulate PKD1 gene dosage and play a role in the initiation of cystogenesis.

Original languageEnglish (US)
Pages (from-to)1941-1948
Number of pages8
JournalJournal of the American Society of Nephrology
Volume23
Issue number12
DOIs
StatePublished - Dec 10 2012

ASJC Scopus subject areas

  • Nephrology

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