title: Activation of the Ca(2+)/calcineurin/NFAT2 pathway controls smooth muscle cell differentiation.
abstract: Cellular mechanisms controlling smooth muscle cells (SMCs) phenotypic modulation are largely unknown. Intracellular Ca2+ movements are essential to ensure SMC functions; one of the roles of Ca2+ is to regulate calcineurin, which in turn induces nuclear localization of the nuclear factor of activated T-cell (NFAT). In order to investigate, during phenotypic differentiation of SMCs, the effect of calcineurin inhibition on NFAT2 nuclear translocation, we used a culture model of SMC differentiation in serum-free conditions. We show that the treatment of cultured SMC with the calcineurin inhibitor cyclosporine A induced their dedifferentiation while preventing their differentiation. These findings suggest that nuclear translocation of NFAT2 is dependent of calcineurin activity during the in vitro SMC differentiation kinetic and that the nuclear presence of NFAT2 is critical in the acquisition and maintenance of SMC differentiation.
authors.affiliation: U441 INSERM, Université Bordeaux 2 Victor Segalen Avenue du Haut Lévêque, 33600 Pessac, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Larrieu
authors.forename: Pierre
authors.initials: P
authors.lastname: Thiébaud
authors.forename: Cécile
authors.initials: C
authors.lastname: Duplàa
authors.forename: Igor
authors.initials: I
authors.lastname: Sibon
authors.forename: Nadine
authors.initials: N
authors.lastname: Thézé
authors.forename: Jean-Marie Daniel
authors.initials: JM
authors.lastname: Lamazière
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D019703:Calcineurin; D002118:Calcium