Neonatal hyperoxic exposure persistently alters lung secretoglobins and annexin A1.

Neonatal hyperoxic exposure persistently alters lung secretoglobins and annexin A1.
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新生儿高氧气暴露持续改变肺促脂蛋白和膜联蛋白A1。

DOI:
10.1155/2013/408485
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发表时间:
2013
影响因子:
--
通讯作者:
Tipple TE
Tipple TE
中科院分区:
生物学3区
文献类型:
--
作者:
Raffay TM;Locy ML;Hill CL;Jindal NS;Rogers LK;Welty SE;Tipple TE

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肺上皮表面功能改变可能与支气管肺发育不良(BPD)婴儿的呼吸系统疾病有关。BPD患儿表现为分泌球蛋白(scgb)表达减少,包括Clara细胞分泌蛋白(CCSP)。在CCSP基因敲除小鼠中,肺SCGB和膜联蛋白A1 (ANXA1)的表达持续改变,表明CCSP间接影响先天免疫反应。目前的研究验证了新生儿高氧暴露诱导CCSP表达缺陷的假设,CCSP表达缺陷与肺SCGB和ANXA1表达的持续改变有关。新生C3H/HeN小鼠从出生起暴露于室内空气(RA)或85% O2中,14 d时处死或返回室内14 d。新生儿高氧后RA恢复与肺CCSP和SCGB3A1蛋白降低有关,但与mRNA表达无关。高氧诱导的ANXA1电荷特性的改变在RA恢复后没有改变,并且与肺巨噬细胞数量升高有关。这些发现支持高氧诱导的Clara细胞功能改变通过影响免疫调节蛋白影响肺先天免疫功能的模型。研究确定CCSP改变影响BPD中scgb、ANXA1和先天免疫反应的机制是有必要的。
Altered functions of the lung epithelial surface likely contribute to the respiratory morbidities in infants with bronchopulmonary dysplasia (BPD). Infants with BPD exhibit decreased expressions of secretoglobins (SCGBs), including Clara cell secretory protein (CCSP). Expression of lung SCGB and annexin A1 (ANXA1) is persistently altered in CCSP knockout mice suggesting that CCSP indirectly influences innate immune responses. The present studies tested the hypothesis that neonatal hyperoxic exposure induces deficits in CCSP expression that are associated with persistent alterations in lung SCGB and ANXA1 expression. Newborn C3H/HeN mice were exposed to room air (RA) or 85% O2 from birth and were sacrificed at 14 d or returned to RA for 14 d. Neonatal hyperoxia followed by RA recovery was associated with decreased lung CCSP and SCGB3A1 protein but not mRNA expression. Hyperoxia-induced alterations in the charge characteristics of ANXA1 were unchanged by RA recovery and were associated with elevated lung macrophage numbers. These findings support a model in which hyperoxia-induced alterations in Clara cell function influence lung innate immune function through effects on immunomodulatory proteins. Studies to determine the mechanism(s) by which CCSP alterations affect SCGBs, ANXA1, and innate immune responses in BPD are warranted.
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