Alteration of the TGF-β/SMAD pathway in intrinsically and UV-induced skin aging

Alteration of the TGF-β/SMAD pathway in intrinsically and UV-induced skin aging
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DOI:
10.1016/j.mad.2004.11.006
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发表时间:
2005-05-01
影响因子:
5.3
通讯作者:
Kim, KH
Kim, KH
中科院分区:
医学3区
文献类型:
--
作者:
Han, KH;Choi, HR;Kim, KH

文献摘要

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为了表征转化生长因子 (TGF-β) 信号传导并确定其与衰老和光老化过程的关联,我们直接比较了体内本质老化和光老化人类皮肤中 TGF-β/SMAD 的表达。通过RNase保护实验和免疫组织化学方法,我们发现老年人前臂(暴露在阳光下)表皮中T beta RII mRNA和蛋白的表达水平显着低于同一个体的上臂内侧(暴露在阳光下)皮肤。在表皮中,老年人固有老化和光老化皮肤中Smad7 mRNA的表达均高于年轻人防晒皮肤,且在光老化表皮中表达升高。与匹配的内在老化皮肤相比,在光老化前臂皮肤的表皮中观察到 pSmad2 免疫反应性降低。与年轻人相比,老年人上臂内侧皮肤的表皮也出现了这种减少。这些结果表明,紫外线诱导的 T beta RII 下调和 Smad7 的协同过度表达可能会触发对 TGF-β 诱导的 Smad2 磷酸化的抑制。 (c) 2004 Elsevier Ireland Ltd. 保留所有权利。
In an effort to characterize transforming growth factor (TGF-beta) signaling and to determine its association with the aging and photoaging processes, we directly compared the expressions of TGF-beta/SMAD in intrinsically aged and photoaged human skin in vivo. By using an RNase protection assay and by immunohistochemistry, we found that the expression levels of T beta RII mRNA and protein in the epidermis of the forearm (sun-exposed) of the elderly were significantly lower than that of the upper-inner arm (sun-protected) skin of the same individual. In the epidermis, the expressions of Smad7 mRNA in both the intrinsically aged and photoaged skin of the elderly were higher than in the sun-protected skin of the young, and this was elevated in the photoaged epidermis. Decreased pSmad2 immunoreactivity was observed in the epidermis of photoaged forearm skin versus matched intrinsically aged skin. This decrease was also found in the epidermis of upper-inner arm skin of the elderly versus the young. These results suggest that the UV-induced down-regulation of T beta RII and the concerted over-expression of Smad7 may trigger the inhibition of the TGF-beta-induced phosphorylation of Smad2. (c) 2004 Elsevier Ireland Ltd. All rights reserved.