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首页> 外文期刊>American Journal of Physiology >Serum-stimulated alpha 1 type IV collagen gene transcription is mediated by TGF-beta and inhibited by estradiol.
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Serum-stimulated alpha 1 type IV collagen gene transcription is mediated by TGF-beta and inhibited by estradiol.

机译：血清刺激的α1IV型胶原基因转录由TGF-β介导，并受雌二醇抑制。

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摘要

We examined the hypothesis that fetal calf serum (FCS) stimulates murine mesangial cell alpha 1 type IV collagen (COL4A1) gene transcription by increasing autocrine production of transforming growth factor-beta (TGF-beta) through a platelet-derived growth factor (PDGF)-dependent mechanisms. PDGF-stimulated COL4A1 gene transcription was inhibited by neutralizing antibody to TGF-beta (119.3 +/- 3.6 vs. 106.0 +/- 6.2 relative luciferase units, expressed as a percentage of control untreated cells, P < 0.003). FCS-stimulated gene transcription was inhibited by neutralizing antibody to PDGF (148.3 +/- 4.1 vs. 136.7 +/- 0.3 relative luciferase units, P < 0.002) and by neutralizing antibody to TGF-beta (148.3 +/- 4.1 vs. 127.1 +/- 3.4 relative luciferase units, P < 0.036). The inhibitory effect of combined treatment with anti-PDGF and anti-TGF-beta antibody on gene transcription was no greater than that of anti-TGF-beta antibody alone [129.5 +/- 0.53 vs. 127.1 +/- 3.4 relative luciferase units, P = not significant (NS)]. FCS-stimulated gene transcription was also inhibited by estradiol (10(-7) M) (148.4 +/- 3.1 vs. 119.4 +/- 8.1 relative luciferase units, P < 0.019). In the presence of estradiol, anti-TGF-beta antibody failed to further reduce serum-stimulated gene transcription (119.4 +/- 8.1 vs. 115.6 +/- 9.8, P = NS), suggesting that estradiol reverses FCS-stimulated COL4A1 gene transcription by antagonizing the actions of TGF-beta. Measurement of type IV collagen synthesis by Western blotting confirmed that the intact gene responded in a manner analogous to the promoter construct.
机译：我们检查了胎牛血清（FCS）通过增加血小板衍生生长因子（PDGF）的自分泌分泌转化生长因子-β（TGF-beta）刺激鼠系膜细胞α1型IV胶原（COL4A1）基因转录的假设。依赖机制。 PDGF刺激的COL4A1基因转录受到中和TGF-β的抗体的抑制（相对荧光素酶单位为119.3 +/- 3.6对106.0 +/- 6.2，表示为未经处理的对照细胞的百分比，P <0.003）。 FCS刺激的基因转录受到PDGF中和抗体的抑制（148.3 +/- 4.1与136.7 +/- 0.3相对荧光素酶单位，P <0.002）和中和TGF-beta的抗体（148.3 +/- 4.1与127.1） +/- 3.4相对荧光素酶单位，P <0.036）。抗PDGF和抗TGF-β抗体联合治疗对基因转录的抑制作用不大于单独抗TGF-β抗体的抑制作用[129.5 +/- 0.53与127.1 +/- 3.4相对荧光素酶单位， P =不重要（NS）]。 FCS刺激的基因转录也被雌二醇（10（-7）M）抑制（相对荧光素酶单位为148.4 +/- 3.1对119.4 +/- 8.1，P <0.019）。在存在雌二醇的情况下，抗TGF-β抗体无法进一步降低血清刺激的基因转录（119.4 +/- 8.1与115.6 +/- 9.8，P = NS），表明雌二醇逆转了FCS刺激的COL4A1基因的转录。通过拮抗TGF-β的作用。通过Western印迹测量IV型胶原蛋白合成，证实完整基因以类似于启动子构建体的方式应答。

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