Glucuronyl C5-epimerase is crucial for epithelial cell maturation during embryonic lung development
Glucuronyl C5-epimerase is crucial for epithelial cell maturation during embryonic lung development
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葡萄糖醛酸 C5-差向异构酶对于胚胎肺发育过程中上皮细胞的成熟至关重要
DOI：
10.1093/glycob/cwaa065
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发表时间：
2021-03-01
期刊：
影响因子：
4.3
通讯作者：
Li, Jin-Ping
中科院分区：
文献类型：
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作者：
Cui, Hao;Cheng, Xiaowen;Li, Jin-Ping
葡萄糖醛酸基C5-差向异构酶(HSEPI)是硫酸肝素生物合成的关键酶，硫酸乙酰肝素是一种表达在细胞表面和肺泡壁及血管细胞外基质中的硫酸盐多糖。在小鼠中定向阻断HSepi基因Glce导致新生儿死亡，这很可能是由于肺不张。在这项研究中，我们研究了肺发育缺陷背后的潜在机制。对胚胎肺的组织学分析表明，在E16.5之前，野生型和突变动物的形态没有差异。这表明，导致肺原基形成和分支形态发生的初始事件没有受到干扰。然而，E17.5-18.5突变体的远端肺仍然由上皮小管组成，缺乏正常E17.5肺的典型囊状结构特征。免疫组织化学染色显示突变鼠肺表面活性蛋白-C信号较强，而T1α信号较弱，提示I型肺泡上皮细胞(AT1)分化受阻。导致AT1成熟失败的参数之一是发育中的肺中血管生成减少。
Glucuronyl C5-epimerase (Hsepi) is a key enzyme in the biosynthesis of heparan sulfate that is a sulfated polysaccharide expressed on the cell surface and in the extracellular matrix of alveolar walls and blood vessels. Targeted interruption of the Hsepi gene, Glce, in mice resulted in neonatal lethality, which is most likely due to lung atelectasis. In this study, we examined the potential mechanisms behind the defect in lung development. Histological analysis of the lungs from embryos revealed no difference in the morphology between wild-type and mutant animals up to E16.5. This suggests that the initial events leading to formation of the lung primordium and branching morphogenesis are not disturbed. However, the distal lung of E17.5-18.5 mutants is still populated by epithelial tubules, lacking the typical saccular structural characteristic of a normal E17.5 lung. Immunostaining revealed strong signals of surfactant protein-C, but a weaker signal of T1 alpha in the mutant lungs in comparison to WT littermates, suggesting differentiation of type I alveolar epithelial cells (AT1) is impaired. One of the parameters contributed to the failure of AT1 maturation is reduced vascularization in the developing lungs.