Dynamics of differentiated-renal epithelial cell monolayer after calcium oxalate injury: The role of cyclooxygenase-2

CASALI, CECILIA I.; PESCIO, LUCILA G.; SENDYK, DYLAN E.; ERJAVEC, LUCIANA C.; MOREL GÓMEZ, EMANUEL; PARRA, LEANDRO G.; FERNÁNDEZ-TOMÉ, MARÍA C.

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2023 vol. 319

0024-3205

Aims: Calcium oxalate (Oxa), constituent of most common kidney stones, damages renal tubular epithelial cellsleading to kidney disease. Most in vitro studies designed to evaluate how Oxa exerts its harmful effects wereperformed in proliferative or confluent non-differentiated renal epithelial cultures; none of them consideredphysiological hyperosmolarity of renal medullary interstitium. Cyclooxygenase 2 (COX2) has been associated toOxa deleterious actions; however, up to now, it is not clear how COX2 acts. In this work, we proposed an in vitroexperimental system resembling renal differentiated-epithelial cells that compose medullary tubular structureswhich were grown and maintained in a physiological hyperosmolar environment and evaluated whether COX2→ PGE2 axis (COX2 considered a cytoprotective protein for renal cells) induces Oxa damage or epithelialrestitution.Main methods: MDCK cells were differentiated with NaCl hyperosmolar medium for 72 h where cells acquired thetypical apical and basolateral membrane domains and a primary cilium. Then, cultures were treated with 1.5 mMOxa for 24, 48, and 72 h to evaluate epithelial monolayer restitution dynamics and COX2-PGE2 effect.Key findings: Oxa completely turned the differentiated phenotype into mesenchymal one (epithelial-mesenchymaltransition). Such effect was partially and totally reverted after 48 and 72 h, respectively. Oxa damage was evendeeper when COX2 was blocked by NS398. PGE2 addition restituted the differentiated-epithelial phenotype in atime and concentration dependence.Significance: This work presents an experimental system that approaches in vitro to in vivo renal epithelial studiesand, more important, warns about NSAIDS use in patients suffering from kidney stones.