Identification of a glucocorticoid response element in the human transforming growth factor beta 1 gene promoter.

Identification of a glucocorticoid response element in the human transforming growth factor beta 1 gene promoter.
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人转化生长因子β1基因启动子中糖皮质激素反应元件的鉴定。

DOI:
10.1016/s1357-2725(98)00005-3
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发表时间:
1998
期刊:
The international journal of biochemistry & cell biology
影响因子:
--
通讯作者:
Cutroneo,KR
Cutroneo,KR
中科院分区:
--
文献类型:
--
作者:
Parrelli,JM;Meisler,N;Cutroneo,KR

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对皮肤伤口愈合具有刺激作用的TGF-β 1被认为是纤维化的主要致病因子。糖皮质激素如地塞米松通常抑制伤口愈合,并能够拮抗TGF-β 1的纤维化作用。我们的数据表明存在一个假定的调节元件响应糖皮质激素。对人TGF-β 1基因启动子区(Genbank登录号J04431)的计算机序列分析显示,在转录起始位点的(− 1081)至(− 1086)碱基对之间存在一个共有糖皮质激素反应元件GRE(5 ′-AGAACA)。获得含有该位点的寡核苷酸并标记用于凝胶迁移率变动测定。发现标记的寡核苷酸结合胎鼠皮肤核提取物和纯化的重组糖皮质激素受体。含有大鼠1型前胶原启动子的GRE或市售GRE的未标记寡核苷酸可与TGF-β 1启动子的32P标记GRE有效竞争结合细胞核提取物。添加抗糖皮质激素受体揭示了标记的阿糖胞苷-核蛋白复合物的超移位。这些结果表明在人TGF-β 1基因的启动子区存在推定的GRE。
TGF-β1, which has a stimulatory effect on dermal wound healing, has been implicated as the primary causative agent of fibrosis. Glucocorticoids such as dexamethasone normally inhibit wound healing and are capable of antagonizing the fibrotic effect of TGF-β1. Our data indicate the presence of a putative regulatory element responsive to glucocorticoids. Computer sequence analysis of the promoter region of the human TGF-β1 gene (Genbank Accession # J04431) revealed a consensus glucocorticoid response element, GRE (5′-AGAACA) located from (−1081) to (−1086) base pairs from the transcription start site. An oligonucleotide containing this site was obtained and labeled for use in gel mobility shift assays. The labeled oligonucleotide was found to bind both fetal rat skin nuclear extracts and purified recombinant glucocorticoid receptor. Unlabeled oligonucleotides containing a GRE from the rat procollagen type 1 promoter or a commercially supplied GRE competed effectively with the32P-labeled GRE from the TGF-β1 promoter for binding to nuclear extracts. Addition of anti-glucocorticoid receptor revealed a supershifting of the labeled oligonucleotide-nuclear protein complex. These results indicate the presence of a putative GRE in the promoter region of the human TGF-β1 gene.
糖皮质激素通过糖皮质激素和转化生长因子β反应元件协调调节I型胶原蛋白proα1启动子活性:糖皮质激素调节真核基因的新机制
DOI: --
发表时间: 1995
影响因子: 4
作者:
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期刊: The Journal of biological chemistry
影响因子: --
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影响因子: 11.4
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