Cellular Physiology and Biochemistry
Original Paper
Lysophosphatidic Acid is a Modulator of Cyst Growth in Autosomal Dominant Polycystic Kidney DiseaseBlazer-Yost B.L.1,4 · Blacklock B.J.2 · Flaig S.1 · Bacallao R.L.3,4 · Gattone V.H.1,41Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis,2Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis,3Division of Nephrology, Indiana University School of Medicine, Indianapolis,4Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis
Bonnie L. Blazer-Yost Biology Department, Indiana University Purdue University at Indianapolis 723 West Michigan Street, Indianapolis, IN 46202 (USA) Tel. +1317-278-1145, Fax +1317-274-2846 E-Mail bblazer@iupui.edu |
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Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the slow growth of multiple fluid-filled cysts predominately in the kidney tubules and liver bile ducts. Elucidation of mechanisms that control cyst growth will provide the basis for rational therapeutic intervention. We used electrophysiological methods to identify lysophosphatidic acid (LPA) as a component of cyst fluid and serum that stimulates secretory Cl- transport in the epithelial cell type that lines renal cysts. LPA effects are manifested through receptors located on the basolateral membrane of the epithelial cells resulting in stimulation of channel activity in the apical membrane. Concentrations of LPA measured in human ADPKD cyst fluid and in normal serum are sufficient to maximally stimulate ion transport. Thus, cyst fluid seepage and/or leakage of vascular LPA into the interstitial space are capable of stimulating epithelial cell secretion resulting in cyst enlargement. These observations are particularly relevant to the rapid decline in renal function in late-stage disease and to the “third hit” hypothesis that renal injury exacerbates cyst growth.
© 2011 S. Karger AG, Basel
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Article / Publication Details
Accepted: November 18, 2011
Published online: December 16, 2011
Issue release date: December 2011
Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0
ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)
For additional information: https://www.karger.com/CPB
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