Transforming growth factor-beta stabilizes elastin mRNA by a pathway requiring active Smads, protein kinase C-delta, and p38.
Transforming growth factor-beta stabilizes elastin mRNA by a pathway requiring active Smads, protein kinase C-delta, and p38.
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DOI：
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发表时间：
2002
影响因子：
6.4
通讯作者：
U. Kucich;J. Rosenbloom;W. Abrams;J. Rosenbloom
中科院分区：
文献类型：
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作者：
U. Kucich;J. Rosenbloom;W. Abrams;J. Rosenbloom
转化生长因子（TGF）-β在其生物活性方面是多能的，调节细胞生长和分化以及细胞外基质沉积和降解。这些活性中的大多数涉及基因转录的调节，但是之前已经显示TGF-β 1通过稳定弹性蛋白原mRNA来显著增加弹性蛋白的表达，所述弹性蛋白原mRNA通过可能涉及磷脂酰胆碱特异性磷脂酶C、蛋白激酶C、异戊烯化和酰化蛋白以及一种或多种酪氨酸激酶的信号传导途径。然而，有一个4- 6小时的滞后期后，加入TGF-β 1之前观察到的弹性蛋白表达的显着刺激和Smads是否参与的问题还没有得到解决。在目前的工作中，使用培养的人胎肺成纤维细胞，我们表明，通过使用特定的抑制剂和转染的Smad 7结构，除了从头蛋白质合成和活性Smads，蛋白激酶C（PKC）-δ和应激活化蛋白激酶，p38的延长活性，是必需的TGF-β 1，以实现弹性蛋白mRNA的稳定。
Transforming growth factors (TGFs)-beta are multipotent in their biologic activity, regulating cell growth and differentiation as well as extracellular matrix deposition and degradation. Most of these activities involve modulation of gene transcription, but TGF-beta1 has been shown previously to substantially increase the expression of elastin by stabilization of tropoelastin mRNA through a signaling pathway that likely involves a phosphatidylcholine-specific phospholipase C, a protein kinase C, prenylated and acylated protein(s), and one or more tyrosine kinases. However, there is a 4- to 6-h lag period after the addition of TGF-beta1 before significant stimulation of elastin expression is observed and the question of whether the Smads are involved has not been addressed. In the present work, using cultured human fetal lung fibroblasts, we show through the use of specific inhibitors and transfection of a Smad 7 construct that in addition to de novo protein synthesis and active Smads, the extended activity of protein kinase C (PKC)-delta and the stress-activated protein kinase, p38, is required for TGF-beta1 to achieve elastin mRNA stabilization.