Unique spatial and cellular expression patterns of Hoxa5, Hoxb4, and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia.
Unique spatial and cellular expression patterns of Hoxa5, Hoxb4, and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia.
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正常发育的小鼠肺中 Hoxa5、Hoxb4 和 Hoxb6 蛋白的独特空间和细胞表达模式在肺发育不全时发生改变。
DOI：
10.1002/bdra.20481
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Chinoy,MalaRomeshchandra
中科院分区：
文献类型：
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作者：
Volpe,MaryAnnVitoria;Wang,KarenTingWai;Nielsen,HeberCarl;Chinoy,MalaRomeshchandra
Hox转录因子调节控制器官形态发生的信号通路，并维持成体细胞的命运和分化。类维生素A信号，调节Hox表达的关键，在肺发育不全中改变。关于Hox蛋白在正常肺发育和肺发育不全中的模式特异性表达的信息很少。我们的目的是确定肺发育不良如何改变Hoxa 5，Hoxb 4和Hoxb 6蛋白的时间，空间和细胞表达与正常肺发育相比。（未处理）和硝苯酰草醚诱导的肺发育不良（NT-PH）从妊娠第13.5天，16，NT-PH肺组织中蛋白质水平的改变以及Hox在空间和细胞中的表达模式与肺发育延迟一致。不同的蛋白质亚型检测到每一个Hox蛋白。Hoxa 5和Hoxb 6蛋白亚型的表达水平随着发育而变化，并在NT-PH肺中进一步改变。与正常肺相比，GD 19和新生儿NT-PH肺的Hoxb 6降低，Hoxa 5和Hoxb 4增加。在正常肺中，Hoxa 5细胞定位较早地从间充质转变为上皮。在整个发育过程中，Hoxb 4在间充质和上皮细胞中表达。Hoxb 6主要存在于远端airways.CONCLUSIONSUnique的空间和细胞表达的Hoxa 5，Hoxb 4，和Hoxb 6参与分支形态发生和终末囊的形成。改变的Hox蛋白表达的时间和细胞平衡有助于肺发育不全或作为一种补偿机制试图纠正这种情况下的异常肺发育和成熟。出生缺陷研究（A部分），2008年。© 2008 Wiley利斯公司
BACKGROUNDHox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern‐specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial, and cellular expression of Hoxa5, Hoxb4, and Hoxb6 proteins compared to normal lung development.METHODSTemporal, spatial, and cellular Hoxa5, Hoxb4, and Hoxb6 expression was studied in normal (untreated) and nitrofen‐induced hypoplastic (NT‐PH) lungs from gestational day 13.5, 16, and 19 fetuses and neonates using Western blot and immunohistochemistry.RESULTSModification of protein levels and spatial and cellular Hox expression patterns in NT‐PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 protein isoforms changed with development and were altered further in NT‐PH lungs. Compared to normal lungs, GD19 and neonatal NT‐PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways.CONCLUSIONSUnique spatial and cellular expression of Hoxa5, Hoxb4, and Hoxb6 participates in branching morphogenesis and terminal sac formation. Altered Hox protein temporal and cellular balance of expression either contributes to pulmonary hypoplasia or functions as a compensatory mechanism attempting to correct abnormal lung development and maturation in this condition. Birth Defects Research (Part A) 2008. © 2008 Wiley‐Liss, Inc.