Prenatal administration of retinoic acid upregulates insulin-like growth factor receptors in the nitrofen-induced hypoplastic lung.
Prenatal administration of retinoic acid upregulates insulin-like growth factor receptors in the nitrofen-induced hypoplastic lung.
复制标题
产前给予视黄酸可上调除草醚诱导的肺发育不全中的胰岛素样生长因子受体。
DOI：
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
P. Puri
中科院分区：
文献类型：
--
作者：
E. Ruttenstock;T. Doi;J. Dingemann;P. Puri
背景
肺发育不全（PH）是新生儿先天性膈疝（CDH）死亡的主要原因。产前给予维甲酸（RA）可刺激除草醚诱导的肺发育不全的肺泡形成。胰岛素样生长因子受体（IGFRs）在肺发育过程中的肺泡形成中起着至关重要的作用。我们最近证明，IGFRs下调，在肺发育的后期阶段，在除草醚CDH模型。几项研究表明RA调节胰岛素样生长因子信号传导的能力。我们假设，IGFRs肺基因表达上调后，在硝苯酰草醚诱导的CDH模型的RA管理。
方法
妊娠大鼠在妊娠第9天（D9）暴露于橄榄油或除草醚。在D18、D19和D20天腹腔内给予RA。于D21取胎肺，分为对照组、对照+ RA组、CDH组和CDH + RA组。RT-PCR和免疫组化检测IGFRs基因和蛋白表达。
结果
与CDH组相比，对照+ RA组和CDH + RA组IGFRs mRNA表达水平均显著升高。与CDH肺组织相比，对照+ RA和CDH + RA肺组织IGFRs的免疫反应性明显增强。
结论
在除草醚模型中，产前RA治疗后IGFRs的肺基因和蛋白表达上调，表明RA可能通过刺激IGFRs介导的肺泡形成来促进肺生长。
BACKGROUND
Pulmonary hypoplasia (PH) is the main cause of mortality in newborns with congenital diaphragmatic hernia (CDH). Prenatal administration of retinoic acid (RA) stimulates alveologenesis in the nitrofen-induced pulmonary hypoplasia. Insulin-like growth factor receptors (IGFRs) play a crucial role in alveologenesis during lung development. We recently demonstrated that IGFRs were downregulated in later stages of lung development in the nitrofen CDH model. Several studies suggest the ability of RA to regulate insulin-like growth factor signaling. We hypothesized that IGFRs pulmonary gene expression is upregulated after the administration of RA in the nitrofen-induced CDH model.
METHODS
Pregnant rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on days D18, D19, and D20. Fetal lungs were dissected on D21 and divided into control, control + RA, CDH, and CDH + RA group. IGFRs gene and protein expression were determined using RT-PCR and immunohistochemistry.
RESULTS
mRNA expression levels of IGFRs were significantly increased in control + RA and CDH + RA compared with CDH group. Immunoreactivity of IGFRs was markedly increased in control + RA and CDH + RA compared with CDH lungs.
CONCLUSIONS
Upregulation of pulmonary gene and protein expression of IGFRs after prenatal RA treatment in the nitrofen model suggests that RA may promote lung growth by stimulating IGFRs mediated alveologenesis.
DOI：
10.1152/ajplung.2000.278.5.l955
发表时间：
2000-05-01
影响因子：
4.9
作者：
Massaro, GD;Massaro, D
通讯作者：
Massaro, D