title: Hypotonic stress induces E-cadherin expression in cultured human keratinocytes.
abstract: Human epidermis marks the interface between internal and external environments with the major task being to maintain body hydration. Alternating exposure of skin to a dry or humid environment is likely to cause changes in the epidermal water gradient resulting in osmotic alterations of epidermal keratinocytes. The present in vitro approach studied the effect of hypotonicity on cell-cell contact. It was demonstrated that hypotonic stress applied to human epithelial cells (HaCaT, A-431) induced upregulation of E-cadherin at both, the protein and mRNA level. 5'-deletional mutants of the E-cadherin promoter identified an element ranging from -53 to +31 that conveyed strong transactivation under hypotonic stress. In order to define relevant upstream regulators members of the MAP kinase family, the epidermal growth factor receptor (EGFR) and protein kinase B/Akt (PKB/Akt) were investigated. Hypotonic conditions led to a fast activation of ERK1/2, SAPK/JNK, p38, EGFR and PKB/Akt with distinct activation patterns. Experiments using specific inhibitors showed that p38 contributes to the E-cadherin transactivation under hypotonic conditions. Further upstream, adhesion was found to be a prerequisite for E-cadherin transactivation in this model. In summary, the present study provides evidence that E-cadherin is an osmo-sensitive gene that responds to hypotonic stress. The function of this regulation may be found in morphological changes induced by cell swelling. It is likely that induction of E-cadherin contributes to the stabilization between adjacent cells in order to withstand the physical forces induced by hypotonicity.
authors.affiliation: Department of Dermatology, University of Frankfurt Medical School, D-60590 Frankfurt/Main, Germany. kippenberger@em.uni-frankfurt.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Kippenberger
authors.forename: Stefan
authors.initials: S
authors.lastname: Loitsch
authors.forename: Maike
authors.initials: M
authors.lastname: Guschel
authors.forename: Jutta
authors.initials: J
authors.lastname: Müller
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: August
authors.initials: A
authors.lastname: Bernd
mesh_terms: D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology; D015603:Keratinocytes / Q000737:chemistry / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009997:Osmotic Pressure; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D020218:Response Elements / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D007038:Hypotonic Solutions; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases