Glucocorticoids coordinately regulate type I collagen proα1 promoter activity through both the glucocorticoid and transforming growth factor β response elements: A novel mechanism of glucocorticoid regulation of eukaryotic genes
Glucocorticoids coordinately regulate type I collagen proα1 promoter activity through both the glucocorticoid and transforming growth factor β response elements: A novel mechanism of glucocorticoid regulation of eukaryotic genes
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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：
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发表时间：
1995
影响因子：
4
通讯作者：
K. Cutroneo
中科院分区：
文献类型：
--
作者：
N. Meisler;S. Shull;Ronglin Xie;G. Long;M. Absher;Joseph P. Connolly;K. Cutroneo
糖皮质激素先前已被证明可以减少体内和成纤维细胞培养物中 1 型胶原蛋白的合成。多项研究表明，糖皮质激素会降低 1 型原胶原基因表达。后面的这些研究包括尿苷掺入 proα1(I) 和 proα2(1) mRNA 以及核径流实验。使用 ColCat 3.6 质粒（包含 proα1 (1) 胶原蛋白基因的 5' 侧翼区域的一部分和报告基因氯霉素乙酰转移酶），本研究通过稳定转染胎鼠皮肤成纤维细胞证明地塞米松下调 proα1(I) 胶原蛋白基因的启动子活性。使用 ColCat 3.6、2.4、1.7 或 0.9 质粒证明了糖皮质激素介导的原胶原基因表达下调。此外，竞争性寡核苷酸转染实验和whoulue ColCat 3.6质粒中糖皮质激素反应元件(GRE)的位点特异性突变并没有消除该效应。糖皮质激素介导的前胶原基因表达下调也可能需要 proα1(I) 胶原蛋白基因 5' 侧翼区域中的另一个顺式元件，因为 TGF-β 已被证明可以刺激胶原蛋白 proα1(I) 和 proα2(I) 基因活性。地塞米松治疗未转染的皮肤成纤维细胞确实导致转化生长因子-β 的减少。通过向培养基中添加外源性 TGF-β，地塞米松导致的 CVAT 活性降低恢复到对照值。凝胶迁移率研究表明，糖皮质激素对大鼠皮肤成纤维细胞的治疗减少了糖皮质激素受体与 GRE 的结合，以及 TGF-β 激活蛋白与 TGF-β 元件的结合，通过协调外源 TGF-β 治疗将其恢复到对照值。因此，这些 TGF-β 分子与细胞膜受体的相互作用以及随后的转导显着减少，导致调节胶原蛋白基因表达的信号减少。这些数据表明糖皮质激素通过 GRE 和 TGF-β 元件协调调节前胶原基因表达。糖皮质激素通过 TGF-β 元件抑制前胶原基因表达是由 TGF-β 分泌减少介导的，可能涉及对非胶原蛋白基因编码的调节蛋白的二次影响。目前的研究为糖皮质激素介导的含有 TGF-β 元件的真核基因调节的新机制提供了基础。 © 1995 Wiley-Liss, Inc.
Glucocorticoids have previously been shown to decrease Type 1 collagen synthesis in vivo and in fibroblast cell culture. Several studies have demonstrated that glucocorticoids decrease Type 1 procollagen gene expression. These latter studies have included uridine incorporation into proα1(I) and proα2(1) mRNas and nuclear run‐off experiments. Using the ColCat 3.6 plasmid, which contains part of the 5' flanking regionof the proα1 (1) coullagen gene and the reporter gene, chljoramphenicol acetyltransferase, the present studies demonstrate by stable transfection of fetal rat skin fibrolblasts that dexamethasone down regulates the promoter activity of the proα1(I) collagen gene. The glucocorticoid‐mediated down‐regulastionof procolljagen gene expression was demonstrated using the ColCat 3.6, 2.4, 1.7, or 0.9 plasmid. In addition, competitive oligonucleotide transfection experiments and site specific mutation of the glucocorticoid response element (GRE) in the whoulue ColCat 3.6 plasmid did not elimiinatre the effect. The ipossibility existed that another cis‐element inthe 5' flanking region of the proα1(I) collagen gene was also required for the glucocorticoid‐mediated down‐regulation of procollagen gene expression, since TGF‐β has been shown to stimulate collagen proα1(I) and proα2(I) gene activities. Dexamethasone treatment of non‐transfected skin fibroblasts did result in a decrease of transforming growth factor‐β. The decrease of CVAT activity by dexamethasone was brought back to control value by the addition of exogenous TGF‐β to the culture media. Gel mobility studies demonstrated that glucocorticoid treatment of rat skin fibroblasts decreased glucocorticoid recptor binding to the GRE and TGF‐β activator protein to the TGF‐β element which were brought back to control values by coordinate exogenous TGF‐β treatment. Thus the interaction of these TGF‐β molecules with cellular membrane receptors and subsequent rtransduction is dramatically decreased resulting in less signals to regulate collagen gene expression. These data indicate that glucocorticoids coordinately regulate procollagen gene expfrssion through both the GRE and TGF‐β elements. Depression of procollagen gene expression by glucocorticoids through the TGF‐β element is mediated by decreased TGF‐β secretion, possibly involving a secondary effect on regulatory protein(s) encoded by noncollagenous protein gene(s). The present studies provide the bassis for a novel mechanism of glucocorticoid‐mediated regulation of eukaryotic genes containing the TGF‐β element. © 1995 Wiley‐Liss, Inc.
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糖皮质激素减少 I 型前胶原 mRNA 的合成。
影响因子：
2.9
作者：
Cockayne,D;SterlingJr,KM;Shull,S;Mintz,KP;Illeyne,S;Cutroneo,KR
通讯作者：
Cutroneo,KR
影响因子：
3.6
作者：
A. Oikarinen;H. Oikarinen;C. Meeker;E. Tan;J. Uitto
通讯作者：
A. Oikarinen;H. Oikarinen;C. Meeker;E. Tan;J. Uitto
DOI：
10.1016/s0021-9258(19)38305-x
发表时间：
1990-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
S. Boast;M. Su;F. Ramirez;M. Sánchez;E. Avvedimento
通讯作者：
S. Boast;M. Su;F. Ramirez;M. Sánchez;E. Avvedimento
两种不同的负调节因子和一种正调节因子与 α 1 (I) 胶原蛋白基因的短启动子片段相互作用。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Karsenty,G;deCrombrugghe,B
通讯作者：
deCrombrugghe,B
DOI：
10.1165/ajrcmb/8.4.417
发表时间：
1993-04-01
影响因子：
6.4
作者：
KELLEY, J;SHULL, S;ABSHER, M
通讯作者：
ABSHER, M