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首页> 外文期刊>American Journal of Physiology >TACE in perinatal mouse lung epithelial cells promotes lung saccular formation
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TACE in perinatal mouse lung epithelial cells promotes lung saccular formation

机译：围产期小鼠肺上皮细胞中的TACE促进肺囊形成

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Tumor necrosis factor-a converting enzyme (TACE) is a cell membrane sheddase, expressed in both developmental lung epithelia and mesenchyme. Global abrogation of TACE results in neonatal lethality and multiple organ developmental abnormalities, including dysplastic lung. To further define the roles of TACE in regulating lung development, lung epithelial and/or mesenchymal specific TACE conditional knockout mice were generated. Blockade of TACE function in developing lung epithelial cells caused reduced saccular formation, decreased cell proliferation, and reduced mid-distal lung epithelial cell differentiation. In contrast, mesenchymal TACE knockout did not have any phenotypic change in developing lung. Simultaneous abrogation of TACE in both lung epithelial and mesenchymal cells did not result in a more severe lung abnormality. Interestingly, these lung-specific TACE conditional knockout mice were not neonatal lethal, and their lung structures were essentially normal after alveolarization. In addition, TACE conditional knockout in developing cardiomyo-cytes resulted in noncompaction of ventricular myocardium, as seen in TACE conventional knockout mice. However, these mice were also not neonatal lethal. In conclusion, lung epithelial TACE is essential for promoting fetal lung saccular formation, but not postnatal lung alveolarization in mice. Because the developmental abnormality of either lung or heart induced by TACE deficiency does not directly lead to neonatal lethality, the neonatal death of TACE conventional knockout mice is likely a result of synergistic effects of multiple organ abnormalities.
机译：肿瘤坏死因子-a转换酶（TACE）是一种细胞膜脱落酶，在发育性肺上皮和间充质中均有表达。全面废除TACE会导致新生儿致死率和多器官发育异常，包括肺发育不良。为了进一步定义TACE在调节肺发育中的作用，生成了肺上皮和/或间充质特异性TACE条件性基因敲除小鼠。在发育中的肺上皮细胞中，TACE功能的阻断导致囊形成减少，细胞增殖减少以及中远端肺上皮细胞分化减少。相比之下，间充质TACE基因敲除在发育中的肺部没有任何表型变化。肺上皮细胞和间充质细胞中同时清除TACE不会导致更严重的肺部异常。有趣的是，这些肺特异性TACE条件性基因敲除小鼠不是新生儿致死的，肺泡化后它们的肺结构基本上是正常的。此外，在TACE常规基因敲除小鼠中可见，发育中的心肌细胞中的TACE条件基因敲除导致心室心肌不紧密。但是，这些小鼠也不具有新生儿致死性。总之，肺上皮TACE对促进胎儿肺囊形成至关重要，但对小鼠出生后的肺泡而言则不是必需的。由于TACE缺乏引起的肺或心脏的发育异常不会直接导致新生儿致死性，因此TACE传统基因敲除小鼠的新生儿死亡很可能是多种器官异常协同作用的结果。

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