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首页> 外文期刊>American Journal of Physiology >Suppression of early growth response factor-1 with egr-1 antisense oligodeoxynucleotide aggravates experimental duodenal ulcers.
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Suppression of early growth response factor-1 with egr-1 antisense oligodeoxynucleotide aggravates experimental duodenal ulcers.

机译：egr-1反义寡聚脱氧核苷酸抑制早期生长反应因子-1加重了实验性十二指肠溃疡。

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摘要

Previously, we demonstrated that cysteamine releases endothelin-1 in the rat duodenal mucosa, followed by increased expression of early growth response factor-1 (egr-1). We hypothesized that egr-1 is a key mediator gene in the multifactorial mechanisms of duodenal ulcer development and healing because its protein, transcription factor product Egr-1, regulates the expression of angiogenic growth factors. We wanted to determine the effect of egr-1 antisense oligonucleotide on cysteamine-induced duodenal ulcers as well as on the expression of bFGF, PDGF, and VEGF, of which synthesis is modulated by Egr-1. An antisense oligonucleotide to egr-1 was used to inhibit the synthesis of Egr-1 and to determine its effect on ulcer formation in the rat model of cysteamine-induced duodenal ulceration. Real-time RT-PCR and Western blot analysis were used to assess the expression of Egr-1 mRNA and protein as well as ERK, bFGF, PDGF, and VEGF. The antisense Egr-1 oligonucleotide inhibited the expression of egr-1 mRNA and protein and increased the duodenal ulcer size from 8.1 +/- 1.8 mm(2) in controls to 20.7 +/- 4.0 mm(2) (P < 0.01). Cysteamine induced phosphorylation of ERK1/2 and enhanced the synthesis of bFGF, PDGF, and VEGF in the preulcerogenic stages of duodenal ulceration, whereas egr-1 antisense oligonucleotide markedly decreased the expression of these growth factors in the duodenal mucosa. We also demonstrated that Egr-1 expression relates to the ulcerogenic effect of cysteamine because these actions were not exerted by the toxic analog ethanolamine. Thus Egr-1 seems to play a critical role in duodenal ulceration because Egr-1 downregulation aggravates experimental duodenal ulcers, most likely through the transcriptional inhibition of bFGF, PDGF, and VEGF synthesis.
机译：以前，我们证明了半胱胺会在大鼠十二指肠粘膜中释放内皮素1，然后增加早期生长反应因子1（egr-1）的表达。我们假设egr-1是十二指肠溃疡发展和愈合的多因素机制中的关键介体基因，因为它的蛋白质，转录因子产物Egr-1调节血管生成生长因子的表达。我们想要确定egr-1反义寡核苷酸对半胱胺诱导的十二指肠溃疡以及bFGF，PDGF和VEGF表达的影响，其合成受Egr-1调节。 egr-1的反义寡核苷酸用于抑制Egr-1的合成，并确定其对半胱胺诱导的十二指肠溃疡大鼠模型中溃疡形成的影响。实时RT-PCR和蛋白质印迹分析用于评估Egr-1 mRNA和蛋白质以及ERK，bFGF，PDGF和VEGF的表达。反义Egr-1寡核苷酸抑制egr-1 mRNA和蛋白质的表达并将十二指肠溃疡的大小从对照组的8.1 ​​+/- 1.8 mm（2）增加到20.7 +/- 4.0 mm（2）（P <0.01）。在十二指肠溃疡的致溃疡前阶段，半胱胺诱导ERK1 / 2磷酸化并增强bFGF，PDGF和VEGF的合成，而egr-1反义寡核苷酸显着降低这些生长因子在十二指肠粘膜中的表达。我们还证明了Egr-1表达与半胱胺的致溃疡作用有关，因为这些作用不是由有毒的类似乙醇胺发挥的。因此，Egr-1似乎在十二指肠溃疡中起关键作用，因为Egr-1下调加重了实验性十二指肠溃疡，最有可能是通过bFGF，PDGF和VEGF合成的转录抑制作用。

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