Coactivation of AP-1 activity and TGF-beta 1 gene expression in the stress response of normal skin cells to ionizing radiation
Coactivation of AP-1 activity and TGF-beta 1 gene expression in the stress response of normal skin cells to ionizing radiation
复制标题
DOI：
10.1038/sj.onc.1201433
复制
发表时间：
1997-08-21
期刊：
影响因子：
8
通讯作者：
Lefaix, JL
中科院分区：
文献类型：
--
作者：
Martin, M;Vozenin, MC;Lefaix, JL
在猪皮肤和体外人成纤维细胞和角化细胞中，研究了电离辐射对AP-1转录因子和tgf - β 1生长因子的激活作用。辐照后3和6h，高剂量γ射线强烈诱导Fos和Jun蛋白及其与AP-1一致序列的结合活性，通过特异性抗体探测发现c-Fos、c-Jun和JunB蛋白存在于凝胶转移复合物中。在辐照后，角质形成细胞和成纤维细胞均表现出AP-1活性升高，正如我们之前发现tgf - β 1参与了辐射引起的皮肤病变的发展，我们也检测了tgf - β 1基因表达，辐照后2和6小时，皮肤中tgf - β 1转录物水平升高，通过免疫染色，发现成纤维细胞、角质形成细胞和内皮细胞中tgf - β 1蛋白水平升高。由于启动子含有AP-1结合位点，因此AP-1活性与tgf - β 1诱导之间的关系得到了解决。含有高亲和力AP-1位点的-365 tgf - β 1启动子片段在辐照后与Jun和Fos蛋白的结合增加，这些结果表明应激诱导的tgf - β 1表达是由AP-1转录因子的激活介导的。
Activation of the AP-1 transcription factor and TGF-beta 1 growth factor by ionizing radiation was studied both in vivo in pig skin, and in vitro in human fibroblasts and keratinocytes, Three and 6h after irradiation, the Fos and Jun proteins and their binding activity to an AP-1 consensus sequence were strongly induced by high doses of gamma-rays, c-Fos, c-Jun and JunB proteins were found to be present in gel-shift complexes by probing with specific antibodies, Both keratinocytes and fibroblasts exhibited heightened AP-1 activity following irradiation, As we previously found that TGF-beta 1 is involved in the development of skin lesions induced by radiation, TGF-beta 1 gene expression was also examined, Two and 6h after irradiation, the levels of TGF-beta 1 transcripts were increased in skin, By immunostaining, TGF-beta 1 protein levels were found to be increased in fibroblasts, keratinocytes and endothelial cells, As promoter contains AP-1 binding sites, between AP-1 activity and TGF-beta 1 induction was addressed, The -365 TGF-beta 1 promoter fragment, which contains a high affinity AP-1 site, exhibited increased binding to Jun and Fos proteins following irradiation, These results suggest that stress-inducible TGF-beta 1 expression is mediated by the activation of AP-1 transcription factor.