Cell type-specific regulation of CCN2 protein expression by PI3K-AKT-FoxO signaling.
Cell type-specific regulation of CCN2 protein expression by PI3K-AKT-FoxO signaling.
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DOI：
10.1007/s12079-009-0055-5
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发表时间：
2009-03
影响因子：
4.1
通讯作者：
Goppelt-Struebe, Margarete
中科院分区：
文献类型：
--
作者：
Samarin, Jana;Cicha, Iwona;Goppelt-Struebe, Margarete
结缔组织生长因子（CTGF、CCN2）的生物活性在导致基因表达的细胞内信号传导水平上受到调节，并受到其细胞外相互作用伙伴的调节，这些相互作用伙伴决定了 CCN2 作用的功能结果。在本概述中，我们总结了数据，这些数据提供了证据，证明主要信号传导途径之一磷脂酰肌醇-3 激酶 (PI3K)-AKT 信号传导在 CCN2 表达调节方面显示出显着的细胞类型依赖性。在平滑肌细胞、成纤维细胞和上皮细胞中，抑制该途径会降低 CCN2 表达或不参与 CCN2 基因表达，具体取决于所使用的刺激。相比之下，在微血管内皮细胞中，PI3K-AKT 信号传导的激活与 CCN2 表达呈负相关。在体外流通系统中暴露于层流的人内皮细胞 (HUVEC) 原代培养物中也观察到了抑制 PI3K-AKT 后 CCN2 的上调。在不同类型的内皮细胞中，受 AKT 负调控的 FoxO 转录因子被认为是 CCN2 基因表达的有效激活剂。在 HUVEC 中，我们观察到 FoxO1 核定位增强与非均匀剪切应力区域 CCN2 蛋白合成增加之间的相关性。这些数据表明 FoxO 蛋白是 CCN2 基因表达的关键调节因子，决定了 PI3K-AKT 激活对 CCN2 调节的影响。简短摘要 磷脂酰肌醇 3 激酶 (PI3K)-AKT 信号传导在 CCN2 表达调节方面显示出显着的细胞类型依赖性。在内皮细胞中，PI3K - AKT 信号传导的激活与 CCN2 表达呈负相关。 FoxO 转录因子受 AKT 负向调节，被认为是 CCN2 基因表达的有效激活剂。本文的在线版本 (doi:10.1007/s12079-009-0055-5) 包含补充材料，可供授权用户使用。
The biological activity of connective tissue growth factor (CTGF, CCN2) is regulated at the level of intracellular signaling leading to gene expression, and by its extracellular interaction partners which determine the functional outcome of CCN2 action. In this overview, we summarize the data which provide evidence that one of the major signaling pathways, phosphatidylinositol-3 kinase (PI3K)–AKT signaling, shows a remarkable cell type-dependence in terms of regulation of CCN2 expression. In smooth muscle cells, fibroblasts, and epithelial cells, inhibition of this pathway either reduced CCN2 expression or was not involved in CCN2 gene expression depending on the stimulus used. In microvascular endothelial cells by contrast, activation of PI3K–AKT signaling was inversely related to CCN2 expression. Upregulation of CCN2 upon inhibition of PI3K–AKT was also observed in primary cultures of human endothelial cells (HUVEC) exposed to laminar flow in an in vitro flow-through system. In different types of endothelial cells, FoxO transcription factors, which are negatively regulated by AKT, were identified as potent activators of CCN2 gene expression. In HUVEC, we observed a correlation between enhanced nuclear localization of FoxO1 and increased synthesis of CCN2 protein in areas of non-uniform shear stress. These data indicate that FoxO proteins are key regulators of CCN2 gene expression which determine the effect of PI3K–AKT activation in terms of CCN2 regulation. Short summary Phosphatidylinositol-3 kinase (PI3K)–AKT signaling shows a remarkable cell type-dependence in terms of regulation of CCN2 expression. In endothelial cells activation of PI3K - AKT signaling was inversely related to CCN2 expression. FoxO transcription factors, which are negatively regulated by AKT, were identified as potent activators of CCN2 gene expression. The online version of this article (doi:10.1007/s12079-009-0055-5) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.0605333103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Gomis, Roger R.;Alarcon, Claudio;Massague, Joan
通讯作者：
Massague, Joan
影响因子：
5.2
作者：
Samarin, Jana;Rehm, Margot;Goppelt-Struebe, Margarete
通讯作者：
Goppelt-Struebe, Margarete
影响因子：
7.3
作者：
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通讯作者：
Franke, Thomas F.
DOI：
10.1152/ajplung.00156.2004
发表时间：
2005-01-01
影响因子：
4.9
作者：
Xie, SP;Sukkar, MB;Chung, KF
通讯作者：
Chung, KF
影响因子：
4.8
作者：
Xia, H;Nho, RS;Henke, CA
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