Activation of the Ca2+/calcineurin/NFAT2 pathway controls smooth muscle cell differentiation

被引:19
作者
Larrieu, D [1 ]
Thiébaud, P [1 ]
Duplàa, C [1 ]
Sibon, I [1 ]
Thézé, N [1 ]
Lamazière, JMD [1 ]
机构
[1] Univ Bordeaux 2, INSERM, U441, F-33600 Pessac, France
关键词
cell culture; transcription factor; differentiation markers; cyclosporine;
D O I
10.1016/j.yexcr.2005.07.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 NFAT(2) 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 NFAT(2) is dependent of calcineurin activity during the in vitro SMC differentiation kinetic and that the nuclear presence of NFAT(2) is critical in the acquisition and maintenance of SMC differentiation. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:166 / 175
页数:10
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