Lysophosphatidic Acid is a Modulator of Cyst Growth in Autosomal Dominant Polycystic Kidney Disease

Bonnie L. Blazer-Yost, Brenda J. Blacklock, Stephanie Flaig, Robert L. Bacallao, Vincent H. Gattone

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1255-1264
Number of pages10
JournalCellular Physiology and Biochemistry
Volume28
Issue number6
DOIs
StatePublished - 2011

Keywords

  • CFTR
  • Cystic fibrosis transmembrane regulator
  • LPA receptors
  • mpkCCD cells

ASJC Scopus subject areas

  • Physiology

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