PPAR Research
Volume 2010, Article ID 274376, 8 pages
http://dx.doi.org/10.1155/2010/274376
Pioglitazone Attenuates Cystic Burden in the PCK Rodent Model of Polycystic Kidney Disease
1Department of Biology, Indiana University Purdue University at Indianapolis, 723 West Michigan Street, Indianapolis, IN 46202, USA
2Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
4Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA
Received 20 August 2010; Accepted 11 October 2010
Academic Editor: Lawrence Serfaty
Copyright © 2010 Bonnie L. Blazer-Yost et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 PPAR agonists such as pioglitazone and rosiglitazone decrease mRNA levels of a transport protein, CFTR (cystic fibrosis transmembrane conductance regulator), and the secretory response to vasopressin in cultured renal cells, it is hypothesized that PPAR 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 PPAR agonists and suggest that this class of drugs may be effective in controlling both renal and hepatic cyst growth and fibrosis in PKD.