Paired-related homeobox gene Prx1 is required for pulmonary vascular development
Paired-related homeobox gene Prx1 is required for pulmonary vascular development
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DOI：
10.1161/01.res.0000130656.72424.20
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发表时间：
2004-06-11
影响因子：
20.1
通讯作者：
Jones, PL
中科院分区：
文献类型：
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作者：
Ihida-Stansbury, K;McKean, DM;Jones, PL
在此，我们证明了配对相关的同源盒基因Prx1是肺血管形成所必需的。最初的研究表明，Prx1定位于胎儿肺间质内分化的内皮细胞（ECs），后来定位于形成血管网络的内皮细胞。为了开始确定Prx1是否促进EC分化，我们转染了全长Prx1 cDNA的胎儿肺中胚层细胞，使其形态转变为内皮样表型。此外，prx1转化的细胞获得了在Matrigel上形成血管网络的能力。因此，Prx1可能通过促进胎儿肺中胚层内的肺EC分化以及随后的血管网络整合而起作用。为了了解Prx1如何参与网络形成，我们重点研究了tenascin-C (TN-C)，一种由Prx1诱导的细胞外基质（ECM）蛋白。免疫细胞化学/组织化学表明，在体内和组织培养中，富含tn - c的ECM围绕着prx1阳性的肺血管网络。此外，抗体阻断研究表明，TN-C是prx1依赖性血管网络在Matrigel上形成所必需的。最后，为了确定这些结果在体内是否相关，我们检测了新生Prx1野生型（+/+）和Prx1缺失型（-/-）小鼠，结果表明Prx1对TN-C的表达和肺血管化至关重要。这些研究为理解Prx1如何控制EC分化及其随后融入功能性肺血管网络提供了一个框架。
Herein, we show that the paired-related homeobox gene, Prx1, is required for lung vascularization. Initial studies revealed that Prx1 localizes to differentiating endothelial cells (ECs) within the fetal lung mesenchyme, and later within ECs forming vascular networks. To begin to determine whether Prx1 promotes EC differentiation, fetal lung mesodermal cells were transfected with full-length Prx1 cDNA, resulting in their morphological transformation to an endothelial-like phenotype. In addition, Prx1-transformed cells acquired the ability to form vascular networks on Matrigel. Thus, Prx1 might function by promoting pulmonary EC differentiation within the fetal lung mesoderm, as well as their subsequent incorporation into vascular networks. To understand how Prx1 participates in network formation, we focused on tenascin-C (TN-C), an extracellular matrix (ECM) protein induced by Prx1. Immunocytochemistry/histochemistry showed that a TN-C-rich ECM surrounds Prx1-positive pulmonary vascular networks both in vivo and in tissue culture. Furthermore, antibody-blocking studies showed that TN-C is required for Prx1-dependent vascular network formation on Matrigel. Finally, to determine whether these results were relevant in vivo, we examined newborn Prx1-wild-type (+/+) and Prx1-null (-/-) mice and showed that Prx1 is critical for expression of TN-C and lung vascularization. These studies provide a framework to understand how Prx1 controls EC differentiation and their subsequent incorporation into functional pulmonary vascular networks.