Neuraminidase-1 is required for the normal assembly of elastic fibers.
Neuraminidase-1 is required for the normal assembly of elastic fibers.
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Neuraminidase-1 是弹性纤维正常组装所必需的。
DOI：
10.1152/ajplung.90346.2008
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Hinek,Alexsander
中科院分区：
文献类型：
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作者：
Starcher,Barry;d'Azzo,Alessandra;Keller,PatrickW;Rao,GottipatiK;Nadarajah,Deepa;Hinek,Alexsander
弹性纤维在经历重复的伸展和回缩循环的组织（例如肺和血管）中的组装取决于原弹性蛋白与微纤维支架的适当相互作用和对齐。在这里，我们描述了神经氨酸酶-1（Neu 1）缺乏对小鼠肺和主动脉弹性蛋白组装的体内组织病理学影响。这些小鼠表现出与Tsk小鼠非常相似的紧皮肤表型。Neu 1-null小鼠的正常分隔在新生小鼠中没有发生，导致在成年小鼠中维持的肺泡扩大。电镜下可见弹性纤维异常发育，光镜下免疫组化染色可见弹性蛋白、纤维蛋白-1、纤维蛋白-2和纤维蛋白-5（Fibulin-5，Fib-5）重叠分布。纤维蛋白原-5纤维在肺泡壁和次级隔嵴的顶端呈弥漫性分布。在新生儿和成人肺中，原纤维蛋白-2沉积也异常。在Neu 1基因敲除小鼠的肺发育中，肌成纤维细胞的分散出现异常，肌成纤维细胞随机分布在肺泡壁周围，而不是集中在弹性蛋白合成部位。Neu 1基因敲除小鼠主动脉的弹性膜较薄，并被肥大的平滑肌细胞分隔，平滑肌细胞周围有过量的含唾液酸的部分。通过锁链素水平测量，Neu 1基因敲除小鼠主动脉中弹性蛋白的浓度显著降低。弹性蛋白原和Fib-5的信使水平正常，提示Neu 1基因敲除小鼠的弹性纤维缺陷是由受损的细胞外组装引起的。
The assembly of elastic fibers in tissues that undergo repeated cycles of extension and recoil, such as the lungs and blood vessels, is dependent on the proper interaction and alignment of tropoelastin with a microfibrillar scaffold. Here, we describe in vivo histopathological effects of neuraminidase-1 (Neu1) deficiency on elastin assembly in the lungs and aorta of mice. These mice exhibited a tight-skin phenotype very similar to the Tsk mouse. Normal septation ofNeu1-null mice did not occur in neonatal mice, resulting in enlarged alveoli that were maintained in adults. The abnormal development of elastic fibers was remarkable under electron microscopy and confirmed by the overlapping distribution of elastin, fibrillin-1, fibrillin-2, and fibulin-5 (Fib-5) by the light microscopy immunostainings. Fib-5 fibers appeared diffuse and unorganized around the alveolar walls and the apex of developing secondary septal crests. Fibrillin-2 deposition was also abnormal in neonatal and adult lungs. Dispersion of myofibroblasts appeared abnormal in developing lungs ofNeu1-null mice, with a random distribution of myofibroblast around the alveolar walls, rather than concentrating at sites of elastin synthesis. The elastic lamellae in the aorta of theNeu1-null mice were thinner and separated by hypertrophic smooth muscle cells that were surrounded by an excess of the sialic acid-containing moieties. The concentration of elastin, as measure by desmosine levels, was significantly reduced in the aorta ofNeu1-null mice. Message levels for tropoelastin and Fib-5 were normal, suggesting the elastic fiber defects inNeu1-null mice result from impaired extracellular assembly.