Impaired distal airway development in mice lacking elastin
Impaired distal airway development in mice lacking elastin
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DOI：
10.1165/ajrcmb.23.3.3906
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发表时间：
2000-09-01
影响因子：
6.4
通讯作者：
Li, DY
中科院分区：
文献类型：
--
作者：
Wendel, DP;Taylor, DG;Li, DY
弹性蛋白是哺乳动物肺部的主要成分，主要存在于肺泡中。肺泡弹性纤维的破坏与成人肺气肿的致病机制有关。这些数据定义了弹性蛋白在成熟肺的结构和功能中的作用，并表明弹性蛋白对于肺泡发生很重要。为了研究弹性蛋白在肺部发育中的作用，我们检查了缺乏弹性蛋白（Eln-/-）的小鼠。出生时，Eln-/-肺的远端气囊扩张形成异常大的空腔。这种表型出现在肺泡弹性蛋白合成和沉积之前，这是一个由肌成纤维细胞介导的过程，并在出生后第 4 天后启动。形态测量分析表明，Eln-/- 小鼠中终末气道分支的围产期发育受到抑制。分支缺陷伴随着较少的远端气囊，并因组织隔膜变薄而扩张，这种情况让人想起肺气肿。肺泡发生前肺实质中的弹性蛋白表达定位于发育中气道周围的间质，支持弹性蛋白在气道分支中的作用。因此，除了在成熟肺的结构和功能中的作用外，弹性蛋白对于肺发育至关重要，并且对于终末气道分支也很重要。
Elastin is a major component of the mammalian lung, predominantly found in the alveoli. Destruction of alveolar elastic fibers is implicated in the pathogenic mechanism of emphysema in adults. These data define a role for elastin in the structure and function of the mature lung, and suggest that elastin is important for alveogenesis. To investigate the role of elastin in lung development, we examined mice lacking elastin (Eln-/-). At birth, the distal air sacs of Eln-/- lungs dilate to form abnormally large cavities. This phenotype appears before the synthesis and deposition of alveolar elastin, a process mediated by myofibroblasts and initiated after postnatal Day 4. Morphometric analyses demonstrate that the perinatal development of terminal airway branches is arrested in Eln-/- mice. The branching defect is accompanied by fewer distal air sacs that are dilated with attenuated tissue septae, a condition reminiscent of emphysema. Elastin expression in the lung parenchyma before alveogenesis is localized to the mesenchyme surrounding the developing airways, supporting a role for elastin in airway branching. Thus, in addition to its role in the structure and function of the mature lung, elastin is essential for pulmonary development and is important for terminal airway branching.