Timing and expression of the Angiopoietin-1/Tie-2 pathway in murine lung development and congenital diaphragmatic hernia (CDH).

Columbia University College of Physicians and Surgeons, New York, NY, USA
Disease Models and Mechanisms (Impact Factor: 4.97). 08/2012; 6(1). DOI: 10.1242/dmm.008821
Source: PubMed


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. 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 may 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. Here we report that Ang-1 appears important to murine lung development, establishing its tissue-level expression and localization patterns at key timepoints. Additionally, our data from a nitrofen/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 (ESE-1), may be responsible for the development of pulmonary hypertension in the setting of CDH.

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    • "Ang-1 is an essential mediator of vascular remodeling and stabilizes endothelial cells. The Ang-1 ligand binds to and phosphorylates Tie-2, a receptor tyrosine kinase expressed by the vascular endothelium, thereby promoting endothelial cell migration and survival [21]. Therefore, cells transfected with a VEGF165-Ang-1 vector are conducive to the mutual coordination and promotion of blood vessel formation. "
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