title: Inducible expression of Snail selectively increases paracellular ion permeability and differentially modulates tight junction proteins.
abstract: Constitutive expression of the transcription factor Snail was previously shown to trigger complete epithelial-mesenchymal transition (EMT). The aim of this study was to determine whether inducible expression of Snail could modify epithelial properties without eliciting full mesenchymal conversion. For this purpose, we expressed mouse Snail (mSnail) cDNA in Madin-Darby canine kidney (MDCK) cells under the control of a doxycycline-repressible transactivator. Inducible expression of Snail did not result in overt EMT but induced a number of phenotypic alterations of MDCK cells, the most significant of which was the absence of fluid-filled blisterlike structures called "domes." To understand the mechanisms responsible for dome suppression, we assessed the effect of mSnail expression on epithelial barrier function. Although mSnail did not alter tight junction (TJ) organization and permeability to uncharged solutes, it markedly decreased transepithelial electrical resistance. In light of these findings, we evaluated the ability of MDCK cell monolayers to maintain ionic gradients and found that expression of mSnail selectively increases Na+ and Cl- permeability. Analysis of the expression of claudins, transmembrane proteins that regulate TJ ionic permeability, showed that mSnail induces a moderate decrease in claudin-2 and a substantial decrease in claudin-4 and -7 expression. Together, these results suggest that induction of mSnail selectively increases the ionic permeability of TJs by differentially modulating the expression of specific claudins.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Rue Michel-Servet 1, CH-1211 Geneva 4, Switzerland.
authors.forename: Fabio
authors.initials: F
authors.lastname: Carrozzino
authors.forename: Priscilla
authors.initials: P
authors.lastname: Soulié
authors.forename: Denise
authors.initials: D
authors.lastname: Huber
authors.forename: Noury
authors.initials: N
authors.lastname: Mensi
authors.forename: Lelio
authors.initials: L
authors.lastname: Orci
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: Eric
authors.initials: E
authors.lastname: Féraille
authors.forename: Roberto
authors.initials: R
authors.lastname: Montesano
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017136:Ion Transport / Q000502:physiology*; D051379:Mice; D000071250:Snail Family Transcription Factors; D013752:Tetracycline / Q000494:pharmacology; D019108:Tight Junctions / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D013752:Tetracycline