Repeated Intrauterine Exposures to Inflammatory Stimuli Attenuated Transforming Growth Factor-β Signaling in the Ovine Fetal Lung
Repeated Intrauterine Exposures to Inflammatory Stimuli Attenuated Transforming Growth Factor-β Signaling in the Ovine Fetal Lung
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DOI：
10.1159/000350548
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发表时间：
2013-01-01
期刊：
影响因子：
2.5
通讯作者：
Kramer, Boris W.
中科院分区：
文献类型：
--
作者：
Collins, Jennifer J. P.;Kallapur, Suhas G.;Kramer, Boris W.
背景资料：支气管肺发育不良（BPD）是早产后最常见的并发症之一，与宫内细菌暴露有关。转化生长因子-β（TGF β）与BPD的发展有关。目的：我们假设不同的和/或多种细菌信号可以在发育中的肺中引起不同的TGF β信号传导反应。研究方法：同期交配的妊娠美利奴母羊在117天和/或121/122天胎龄（GA）时接受脂多糖（LPS）和/或微小脲原体血清型3（UP）羊膜内注射。对照组接受等量的生理盐水和/或培养基注射。在124天GA（期限= 150天GA）时对羔羊实施安乐死。检测肺组织中TGF β 1、TGF β 2、TGF β 3、TGF β受体（R）1和TGF β R2蛋白水平、Smad 2磷酸化和弹性蛋白沉积。结果如下：在UP+LPS联合暴露后，总TGF β 1和TGF β 2降低了24%和51%，而在LPS暴露7天后，总TGF β 1增加了31%，但在双重暴露后没有增加。UP后，TGF β R2的肺泡表达降低了75%，但在双重暴露后保持不变。减少局灶性弹性蛋白沉积后，单次LPS暴露，防止双重曝光。结论：TGF β信号成分和弹性蛋白对宫内LPS和UP暴露的反应不同。多次细菌暴露减弱了TGF β信号传导并使弹性蛋白沉积正常化。版权所有（c）2013 S. Karger AG，巴塞尔
Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-beta (TGF beta) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGF beta signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGF beta 1, TGF beta 2, TGF beta 3, TGF beta receptor (R) 1 and TGF beta R2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGF beta 1 and TGF beta 2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGF beta 1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGF beta R2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGF beta signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGF beta signaling and normalized elastin deposition. Copyright (c) 2013 S. Karger AG, Basel