Pioglitazone attenuates cystic burden in the PCK rodent model of polycystic kidney disease

Bonnie L. Blazer-Yost, Julie Haydon, Tracy Eggleston-Gulyas, Jey Hsin Chen, Xiaofang Wang, Vincent Gattone, Vicente E. Torres

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Polycystic kidney disease (PKD) is a genetic disorder characterized by growth of fluid-filled cysts predominately in kidney tubules and liver bile ducts. Currently, the clinical management of PKD is limited to cyst aspiration, surgical resection or organ transplantation. Based on an observation that PPARγ agonists such as pioglitazone and rosiglitazone decrease mRNA levels of a Cl- transport protein, CFTR (cystic fibrosis transmembrane conductance regulator), and the Cl- secretory response to vasopressin in cultured renal cells, it is hypothesized that PPARγ agonists will inhibit cyst growth. The current studies show that a 7- or 14-week pioglitazone feeding regimen inhibits renal and hepatic bile duct cyst growth in the PCK rat, a rodent model orthologous to human PKD. These studies provide proof of concept for the mechanism of action of the PPARγ agonists and suggest that this class of drugs may be effective in controlling both renal and hepatic cyst growth and fibrosis in PKD.

Original languageEnglish (US)
Article number274376
JournalPPAR Research
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology (medical)

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