Thioredoxin-interacting protein inhibits hypoxia-inducible factor transcriptional activity.
Thioredoxin-interacting protein inhibits hypoxia-inducible factor transcriptional activity.
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DOI：
10.1016/j.freeradbiomed.2010.07.016
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发表时间：
2010-11-15
影响因子：
7.4
通讯作者：
Tipple, Trent E.
中科院分区：
文献类型：
--
作者：
Farrell, Michael R.;Rogers, Lynette K.;Liu, Yusen;Welty, Stephen E.;Tipple, Trent E.
关键词：
血管内皮生长因子(VEGF)是肺正常发育所必需的，受低氧诱导因子(HIF)转录调控。先前在新生小鼠支气管肺发育不良(BPD)模型中的发现表明，硫氧还蛋白相互作用蛋白(TXNIP)是一种新的血管内皮生长因子表达调节因子。本研究旨在验证TXNIP通过影响HIF介导的基因表达而负向调节血管内皮细胞生长因子的假设。为了验证这一假设，我们首先检测了出生1天的新生儿和E19胚胎肺中血管内皮生长因子和血栓素NIP蛋白的水平，并检测到显著的负相关。为了阐明这种关系的机制，我们利用小鼠肺上皮细胞(MLE-12)研究了TXNIP过表达对HIF介导的转录的影响。TXNIP的过表达抑制了缺氧和室内空气中HIF介导的报告活性。TXNIP对HIF活性的抑制似乎与TXNIP与硫氧还蛋白结合的能力无关。因此，我们的研究支持一种模型，在该模型中，TXNIP是HIF介导的小鼠肺基因转录的潜在关键调节因子。TXNIP表达的改变可能改变早产儿肺血管内皮生长因子的表达，从而参与BPD的发生发展。
Vascular endothelial growth factor (VEGF) is required for proper lung development and is transcriptionally regulated in alveolar epithelial cells by hypoxia inducible factor (HIF). Previous findings in a newborn mouse model of bronchopulmonary dysplasia (BPD) suggest that thioredoxin interacting protein (Txnip) is a novel regulator of VEGF expression. The present studies were designed to test the hypothesis that Txnip negatively regulates VEGF through effects on HIF-mediated gene expression. To test this hypothesis, we first examined the levels of VEGF and Txnip protein in the lungs of 1 day-old newborn and E19 embryos and detected a significant inverse correlation. To elucidate the mechanisms underlying this relationship, we studied the effects of Txnip overexpression on HIF-mediated transcription using murine lung epithelial (MLE-12) cells. Overexpression of Txnip inhibited HIF-mediated reporter activity in both hypoxia and room air. Suppression of HIF activity by Txnip appeared to be independent of the ability of Txnip to bind to thioredoxin. Thus, our studies support a model in which Txnip is a potentially critical regulator of HIF-mediated gene transcription in the murine lung. Alterations in Txnip expression could alter lung VEGF expression in prematurely born human infants and contribute to the development of BPD.
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影响因子：
11.4
作者：
Ema, M;Hirota, K;Fujii-Kuriyama, Y
通讯作者：
Fujii-Kuriyama, Y
影响因子：
4.8
作者：
Patwari, Parth;Chutkow, William A.;Lee, Richard T.
通讯作者：
Lee, Richard T.
DOI：
10.1165/ajrcmb.27.2.4703
发表时间：
2002-08-01
影响因子：
6.4
作者：
Galambos, C;Ng, YS;deMello, DE
通讯作者：
deMello, DE
影响因子：
37.8
作者：
Thébaud, B;Ladha, F;Archer, SL
通讯作者：
Archer, SL
影响因子：
82.9
作者：
Compernolle, V;Brusselmans, K;Carmeliet, P
通讯作者：
Carmeliet, P