title: Ouabain promotes partial epithelial to mesenchymal transition (EMT) changes in human autosomal dominant polycystic kidney disease (ADPKD) cells.
abstract: The hormone ouabain has been shown to enhance the cystic phenotype of autosomal dominant polycystic kidney disease (ADPKD). Among other characteristics, the ADPKD phenotype includes cell de-differentiation and epithelial to mesenchymal transition (EMT). Here, we determined whether physiological concentrations of ouabain induces EMT in human renal epithelial cells from patients with ADPKD. We found that ADPKD cells respond to ouabain with a decrease in expression of the epithelial marker E-cadherin and increase in the expression of the mesenchymal markers N-cadherin, α smooth muscle actin (αSMA) and collagen-I; and the tight junction protein occludin and claudin-1. Other adhesion molecules, such as ZO-1, β-catenin and vinculin were not significantly modified by ouabain. At the cellular level, ouabain stimulated ADPKD cell migration, reduced cell-cell interaction, and the ability of ADPKD cells to form aggregates. Moreover, ouabain increased the transepithelial electrical resistance of ADPKD cell monolayers, suggesting that the paracellular transport pathway was preserved in the cells. These effects of ouabain were not observed in normal human kidney (NHK) cells. Altogether these results show a novel role for ouabain in ADPKD, inducing changes that lead to a partial EMT phenotype in the cells. These effects further support the key role that ouabain has as a factor that promotes the cystic characteristics of ADPKD cells.
authors.affiliation: Departments of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States; The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Venugopal
authors.affiliation: Departments of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: McDermott
authors.affiliation: Departments of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States; The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, United States.
authors.forename: Gladis
authors.initials: G
authors.lastname: Sanchez
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States; The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, United States.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Laboratório de Bioquímica Celular, Universidade Federal de São João del Rei, Divinopolis, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Barbosa
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States; The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, United States.
authors.forename: Gail A
authors.initials: GA
authors.lastname: Reif
authors.affiliation: Departments of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States; The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, United States.
authors.forename: Darren P
authors.initials: DP
authors.lastname: Wallace
authors.affiliation: Departments of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States; The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, United States. Electronic address: gblanco@kumc.edu.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Blanco
mesh_terms: D000328:Adult; D000368:Aged; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010042:Ouabain / Q000494:pharmacology*; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism / Q000473:pathology*; D013329:Structure-Activity Relationship
chemical_list: D010042:Ouabain
keywords: Adhesion molecule; K-ATPase signaling; Na; Polycystic kidney disease