Semaphorin 3A contributes to distal pulmonary epithelial cell differentiation and lung morphogenesis.
Semaphorin 3A contributes to distal pulmonary epithelial cell differentiation and lung morphogenesis.
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DOI：
10.1371/journal.pone.0027449
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
McGrath-Morrow S
中科院分区：
文献类型：
--
作者：
Becker PM;Tran TS;Delannoy MJ;He C;Shannon JM;McGrath-Morrow S
Semaphorin 3A（Sema 3A）是一种神经导向因子，也介导细胞迁移、增殖和凋亡，并抑制分支形态发生。因为我们已经表明，编码强制性Sema 3A共受体的神经纤毛蛋白-1的基因缺失会影响烟雾暴露的成人肺中的空域重塑，所以我们试图确定Sema 3A的基因缺失是否改变了远端肺结构。为了确定Sema 3A信号传导的丧失是否影响远端肺形态，我们比较了来自具有Sema 3A靶向遗传缺失（Sema 3A-/-）和野生型（Sema 3A +/+）同窝对照的小鼠的肺组织学、远端上皮细胞形态和成熟以及肺细胞增殖和死亡之间的平衡。Sema 3A基因缺失导致围产期死亡。在E17.5，来自Sema 3A-/-小鼠的肺具有增厚的隔膜和减小的空气空间尺寸。远端肺上皮细胞的细胞内糖原池增加，小的多泡体和板层体具有非典型的超微结构，以及I型肺泡上皮细胞标志物的表达减少。在存活于围产期的罕见Sema 3A-/-小鼠的肺中，肺泡化显著减弱。此外，Sema 3A缺失与出生后肺泡间隔细胞死亡增加有关。这些数据表明，Sema 3A调节远端肺上皮细胞发育和肺泡分隔。确定Sema 3A如何影响发育中的肺的结构可塑性是确定是否可以利用这一途径来开发急性或慢性肺损伤后修复的创新策略的关键第一步。
Semaphorin 3A (Sema3A) is a neural guidance cue that also mediates cell migration, proliferation and apoptosis, and inhibits branching morphogenesis. Because we have shown that genetic deletion of neuropilin-1, which encodes an obligatory Sema3A co-receptor, influences airspace remodeling in the smoke-exposed adult lung, we sought to determine whether genetic deletion of Sema3A altered distal lung structure. To determine whether loss of Sema3A signaling influenced distal lung morphology, we compared pulmonary histology, distal epithelial cell morphology and maturation, and the balance between lung cell proliferation and death, in lungs from mice with a targeted genetic deletion of Sema3A (Sema3A-/-) and wild-type (Sema3A+/+) littermate controls. Genetic deletion of Sema3A resulted in significant perinatal lethality. At E17.5, lungs from Sema3A-/- mice had thickened septae and reduced airspace size. Distal lung epithelial cells had increased intracellular glycogen pools and small multivesicular and lamellar bodies with atypical ultrastructure, as well as reduced expression of type I alveolar epithelial cell markers. Alveolarization was markedly attenuated in lungs from the rare Sema3A-/- mice that survived the immediate perinatal period. Furthermore, Sema3A deletion was linked with enhanced postnatal alveolar septal cell death. These data suggest that Sema3A modulates distal pulmonary epithelial cell development and alveolar septation. Defining how Sema3A influences structural plasticity of the developing lung is a critical first step for determining if this pathway can be exploited to develop innovative strategies for repair after acute or chronic lung injury.
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影响因子：
4.6
作者：
Martis, PC;Whitsett, JA;Ikegami, M
通讯作者：
Ikegami, M
影响因子：
8
作者：
Dang, TP;Eichenberger, S;Carbone, DP
通讯作者：
Carbone, DP
影响因子：
16.2
作者：
Feiner, L;Koppel, AM;Raper, JA
通讯作者：
Raper, JA
DOI：
10.1074/jbc.m804595200
发表时间：
2008-10-24
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Giordano RJ;Lahdenranta J;Zhen L;Chukwueke U;Petrache I;Langley RR;Fidler IJ;Pasqualini R;Tuder RM;Arap W
通讯作者：
Arap W
影响因子：
25
作者：
Chen, H;He, ZG;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M