Mesodermal Pten inactivation leads to alveolar capillary dysplasia- like phenotype.
Mesodermal Pten inactivation leads to alveolar capillary dysplasia- like phenotype.
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中胚层 Pten 失活导致肺泡毛细血管发育不良样表型
DOI：
10.1172/jci61334
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Bellusci
中科院分区：
文献类型：
--
作者：
Tiozzo;Carraro;Al Alam;Baptista;Danopoulos;Lavarreda-Pearce;De Langhe;Bellusci
肺泡毛细血管发育不良(ACD)是一种先天性的、致命性的肺血管疾病。10号染色体缺失的磷酸酶和张力蛋白同源物(Pten)编码一种控制关键细胞功能的脂磷酸酶，包括干/祖细胞的增殖和分化；然而，PTEN在中胚层肺细胞谱系形成中的作用仍未被研究。为了确定中胚层PTEN在肺发育过程中不同间充质细胞系个体发育中的作用，我们在小鼠早期胚胎肺间充质中特异性地缺失了Ptenin。幼崽在出生时就死亡了，有证据表明血液氧合功能不佳。细胞水平的分析显示，血管母细胞向内皮细胞分化的缺陷，以及伴随而来的血管母细胞群的聚集，这与无序的毛细血管床有关。我们还发现与ACD人类表型相关的基因叉头盒蛋白F1(Foxf1)的表达减少。对人类ACD样本的分析显示，PTEN显著减少，活化蛋白激酶B(AKT)增加。这些研究表明，中胚层PTEN在控制血管母细胞的扩增和向内皮细胞分化的过程中起着关键作用，从而指导了功能气体交换界面的建立。此外，这些小鼠可以作为ACD的小鼠模型。
Alveolar capillary dysplasia (ACD) is a congenital, lethal disorder of the pulmonary vasculature. Phosphatase and tensin homologue deleted from chromosome 10 (Pten) encodes a lipid phosphatase controlling key cellular functions, including stem/progenitor cell proliferation and differentiation; however, the role of PTEN in mesodermal lung cell lineage formation remains unexamined. To determine the role of mesodermal PTEN in the ontogeny of various mesenchymal cell lineages during lung development, we specifically deletedPtenin early embryonic lung mesenchyme in mice. Pups lackingPtendied at birth, with evidence of failure in blood oxygenation. Analysis at the cellular level showed defects in angioblast differentiation to endothelial cells and an accompanying accumulation of the angioblast cell population that was associated with disorganized capillary beds. We also found decreased expression of Forkhead box protein F1 (Foxf1), a gene associated with the ACD human phenotype. Analysis of human samples for ACD revealed a significant decrease in PTEN and increased activated protein kinase B (AKT). These studies demonstrate that mesodermal PTEN has a key role in controlling the amplification of angioblasts as well as their differentiation into endothelial cells, thereby directing the establishment of a functional gas exchange interface. Additionally, these mice could serve as a murine model of ACD.
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影响因子：
30.8
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
De Langhe, Stijn P.
DOI：
10.1165/rcmb.2005-0024oc
发表时间：
2005
影响因子：
6.4
作者：
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通讯作者：
A. Fine