National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.
J Pediatr Surg. 2011 Jan;46(1):62-6. doi: 10.1016/j.jpedsurg.2010.09.059.
BACKGROUND/PURPOSE: Iroquois homeobox (Irx) genes have been implicated in the early lung morphogenesis of vertebrates. Irx1-3 and Irx5 gene expression is seen in fetal lung in rodents up to day (D) 18.5 of gestation. Fetal lung in Irx knockdown mice shows loss of mesenchyme and dilated airspaces, whereas nitrofen-induced hypoplastic lung displays thickened mesenchyme and diminished airspaces. We hypothesized that the Irx genes are up-regulated during early lung morphogenesis in the nitrofen-induced hypoplastic lung.
Pregnant rats were exposed either to olive oil or nitrofen on D9. Fetal lungs harvested on D15 were divided into control and nitrofen groups; and the lungs harvested on D18 were divided into control, nitrofen without congenital diaphragmatic hernia (CDH[-]), and nitrofen with CDH (CDH[+]). Irx gene expression levels were analyzed by reverse transcriptase polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression of Irx family.
Pulmonary Irx1-3 and Irx5 messenger RNA expression levels were significantly up-regulated in nitrofen group compared with controls at D15. On D15, Irx immunoreactivity was increased in nitrofen-induced hypoplastic lung compared with controls.
Overexpression of Irx genes in the early lung development may cause pulmonary hypoplasia in the nitrofen CDH model by inducing lung dysmorphogenesis with thickened mesenchyme and diminished airspaces.
背景/目的： 同源异形盒基因 Irx 已被牵涉到脊椎动物早期肺形态发生中。在啮齿类动物的胎肺中，Irx1-3 和 Irx5 基因的表达可见于妊娠第 18.5 天（D）之前。Irx 敲低小鼠的胎肺显示出间质缺失和肺泡扩张，而硝呋太尔诱导的肺发育不良显示出间质增厚和肺泡减少。我们假设 Irx 基因在硝呋太尔诱导的肺发育不良的早期肺形态发生中上调。
在 D9 时，给怀孕的大鼠暴露于橄榄油或硝呋太尔。在 D15 收获胎肺，分为对照组和硝呋太尔组；在 D18 收获的胎肺分为对照组、无先天性膈疝（CDH[-]）的硝呋太尔组和有 CDH（CDH[+]）的硝呋太尔组。通过逆转录聚合酶链反应分析 Irx 基因的表达水平。进行免疫组织化学染色以评估 Irx 家族蛋白的表达。
在 D15 时，与对照组相比，硝呋太尔组的肺 Irx1-3 和 Irx5 信使 RNA 表达水平显著上调。在 D15 时，与对照组相比，硝呋太尔诱导的肺发育不良中的 Irx 免疫反应性增加。
Irx 基因在早期肺发育中的过度表达可能通过诱导肺发育不良，导致间质增厚和肺泡减少，从而引起硝呋太尔 CDH 模型中的肺发育不良。
