Inactivation of the Wnt/β-catenin signaling contributes to the epithelial barrier dysfunction induced by sodium oxalate in canine renal epithelial cells
- 21 September 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Animal Science
- Vol. 99 (10)
- https://doi.org/10.1093/jas/skab268
Abstract
High oxalate consumption has been recognized as a risk factor for renal calcium oxalate stones in companion animals (dogs and cats). However, the cellular signaling involved in oxalate-induced dysfunction in renal tubular epithelial cells remains not fully elucidated. In this study, Mardin-Darby canine kidney (MDCK) cells, an epithelial cell line derived from canine kidney tubule, were tested for cell proliferation activity and barrier function after being exposed to sodium oxalate (NaOx). Further, the involvement of Wnt/β-catenin in NaOx-induced renal epithelial barrier dysfunction was evaluated. MDCK cells treated with NaOx exhibited reduction in cell proliferation and migration. Besides, NaOx exposure led to a decrease in transepithelial electrical resistance (TEER) and an increase in paracellular permeability. The deleterious effects of NaOx on epithelial barrier function were related to the suppressed abundance of tight junction proteins including zonula occludens (ZOs), occludin, and claudin-1. Of note, protein levels of β-catenin and p-β-catenin (Ser552) in MDCK cells were repressed by NaOx, indicating inhibitory effects on Wnt/β-catenin signaling. An inhibition of GSK-3β enhanced the abundance of β-catenin and p-β-catenin (Ser552), and protected against epithelial barrier dysfunction in NaOx-treated MDCK cells. The results revealed a critical role of Wnt/β-catenin signaling in the epithelial barrier function of MDCK cells. Activation of Wnt/β-catenin signaling might be a potentially therapeutic target for the treatment of oxalate-linked renal stones.Keywords
Funding Information
- National Natural Science Foundation of China (31625025)
- Jinxinnong Animal Science Development Foundation
This publication has 31 references indexed in Scilit:
- Claudins and the Modulation of Tight Junction PermeabilityPhysiological Reviews, 2013
- p38 MAPK mediates calcium oxalate crystal-induced tight junction disruption in distal renal tubular epithelial cellsScientific Reports, 2013
- The -Catenin Destruction ComplexCold Spring Harbor Perspectives in Biology, 2012
- Stones in cats and dogs: What can be learnt from them?Arab Journal of Urology, 2012
- Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cellsLaboratory Investigation, 2011
- Phosphorylation of AKT/PKB by CK2 is necessary for the AKT-dependent up-regulation of β-catenin transcriptional activityJournal of Cellular Physiology, 2010
- Exploration des fonctions tubulaires rénalesNephrologie & Therapeutique, 2009
- Crystals cause acute necrotic cell death in renal proximal tubule cells, but not in collecting tubule cellsKidney International, 2005
- Oxalate inhibits renal proximal tubule cell proliferation via oxidative stress, p38 MAPK/JNK, and cPLA2signaling pathwaysAmerican Journal of Physiology-Cell Physiology, 2004
- Effects of Oxalate 0n HK-2 Cells, a Line of Proximal Tubular Epithelial Cells From Normal Human KidneyJournal of Urology, 2002