Timing and expression of the angiopoietin-1-Tie-2 pathway in murine lung development and congenital diaphragmatic hernia.
Timing and expression of the angiopoietin-1-Tie-2 pathway in murine lung development and congenital diaphragmatic hernia.
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DOI：
10.1242/dmm.008821
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发表时间：
2013-01
影响因子：
4.3
通讯作者：
Arkovitz MS
中科院分区：
文献类型：
--
作者：
Grzenda A;Shannon J;Fisher J;Arkovitz MS
先天性腹股沟疝（CDH）是最常见的先天性畸形之一。先天性先天性心脏病患儿患有多种合并症，其中最严重的是肺泡发育不良和肺血管高压引起的呼吸功能不全。所有先天性先天性心脏病患儿都表现出一定程度的肺动脉高压，其严重程度与死亡率相关。对CDH肺动脉高压发生的分子机制仍知之甚少。血管生成素-1（Angiopoitein-1，Ang-1）是血管生成的重要介质，参与包括肺在内的多种组织的血管发育。尽管既往研究表明Ang-1可能在家族性肺动脉高压的发生发展中发挥重要作用，但Ang-1在CDH相关肺动脉高压发生发展中的作用尚不清楚。本研究的目的是研究血管紧张素-1通路在CDH小鼠模型中的作用。在这里，我们报告说，血管紧张素-1出现在正常小鼠肺发育的重要性，并已建立其组织水平的表达和定位模式在关键的时间点。此外，我们的数据从除草醚和bisdiamine诱导的小鼠模型的CDH表明，改变表达模式的Ang-1，其受体Tie-2和它的转录因子之一（上皮特异性Ets转录因子1）可能是负责发展的肺血管病变中看到的设置CDH。
Congenital diaphragmatic hernia (CDH) is one of the most common congenital abnormalities. Children born with CDH suffer a number of co-morbidities, the most serious of which is respiratory insufficiency from a combination of alveolar hypoplasia and pulmonary vascular hypertension. All children born with CDH display some degree of pulmonary hypertension, the severity of which has been correlated with mortality. The molecular mechanisms responsible for the development of pulmonary hypertension in CDH remain poorly understood. Angiopoitein-1 (Ang-1), a central mediator in angiogenesis, participates in the vascular development of many tissues, including the lung. Although previous studies have demonstrated that Ang-1 might play an important role in the development of familial pulmonary hypertension, the role of Ang-1 in the development of the pulmonary hypertension associated with CDH is poorly understood. The aim of this study was to examine the role of the Ang-1 pathway in a murine model of CDH. Here, we report that Ang-1 appears important in normal murine lung development, and have established its tissue-level expression and localization patterns at key time-points. Additionally, our data from a nitrofen and bisdiamine-induced murine model of CDH suggests that altered expression patterns of Ang-1, its receptor Tie-2 and one of its transcription factors (epithelium-specific Ets transcription factor 1) might be responsible for development of the pulmonary vasculopathy seen in the setting of CDH.
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DOI：
10.1002/bdra.20613
发表时间：
2010-01-01
影响因子：
--
作者：
Clugston, Robin D.;Zhang, Wei;Greer, John J.
通讯作者：
Greer, John J.
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
4.1
作者：
Mondrinos, Mark J.;Koutzaki, Sirma H.;Finck, Christine M.
通讯作者：
Finck, Christine M.
影响因子：
158.5
作者：
Du, Lingling;Sullivan, Christopher C.;Thistlethwaite, Patricia A.
通讯作者：
Thistlethwaite, Patricia A.
影响因子：
64.5
作者：
Suri, C;Jones, PF;Yancopoulos, GD
通讯作者：
Yancopoulos, GD