Pbx1, Meis1, and Runx1 Expression Is Decreased in the Diaphragmatic and Pulmonary Mesenchyme of Rats with Nitrofen-Induced Congenital Diaphragmatic Hernia
Pbx1, Meis1, and Runx1 Expression Is Decreased in the Diaphragmatic and Pulmonary Mesenchyme of Rats with Nitrofen-Induced Congenital Diaphragmatic Hernia
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硝基芬诱发先天性膈疝大鼠膈肌和肺间质中 Pbx1、Meis1 和 Runx1 表达降低
DOI：
10.1055/s-0040-1714736
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发表时间：
2020
影响因子：
1.8
通讯作者：
Puri Prem
中科院分区：
文献类型：
--
作者：
Takahashi Toshiaki;Friedmacher Florian;Zimmer Julia;Puri Prem
前言先天性腹股沟疝（CDH）和相关的肺发育不全（PH）被认为起源于胸膜腹膜襞（PPF）和原始肺的间充质缺陷。前B细胞白血病同源盒1（Pbx 1）、其结合伴侣骨髓嗜亲性整合位点1（Meis 1）和侏儒相关转录因子1（Runx 1）在横隔膜和肺间充质中表达，充当调节间充质细胞增殖的转录辅因子。此外，Pbx 1 −/−小鼠会出现类似于人类CDH的神经缺陷和PH。我们假设，atmatic和pulmonaryPbx 1，Meis 1，andRunx 1的表达降低在硝苯草醚诱导的CDHmodel.Materials和MethodsTime-mated大鼠暴露于硝苯草醚或车辆在妊娠第9天（D9）。在D13、D15和D18显微解剖胎儿横膈膜（n= 72）和肺（n= 48），并将其分为对照组和暴露于除草醚的标本。通过实时定量聚合酶链反应分析膈肌和肺部Pbx 1、Meis 1和Runx 1基因表达水平。免疫荧光双染色为Pbx 1，Meis 1，和Runx 1与间充质/生肌标志物Gata 4和myogenin相结合，以评估蛋白质expression. ResultsPbx 1，Meis 1，和Runx 1的相对mRNA表达显着降低PPF（D13），发展中的隔膜/肺（D15），肌化隔膜/分化的肺（D18）与对照组相比，除草醚暴露的胎儿。共聚焦激光扫描显微镜显示，与对照组相比，暴露于D13、D15和D18的胎鼠肺和肺间质中Pbx 1、Meis 1和Runx 1的免疫荧光显著减少，与间质细胞增殖减少有关。导致PPF畸形和气道分支中断，从而导致除草醚诱导的CDH模型中的气道缺陷和PH。
IntroductionCongenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia (PH) are thought to originate from mesenchymal defects in pleuroperitoneal folds (PPFs) and primordial lungs. Pre-B-cell leukemia homeobox 1 (Pbx1), its binding partner myeloid ecotropic integration site 1 (Meis1), and runt-related transcription factor 1 (Runx1) are expressed in diaphragmatic and lung mesenchyme, functioning as transcription cofactors that modulate mesenchymal cell proliferation. Furthermore,Pbx1−/−mice develop diaphragmatic defects and PH similar to human CDH. We hypothesized that diaphragmatic and pulmonaryPbx1,Meis1, andRunx1expression is decreased in the nitrofen-induced CDH model.Materials and MethodsTime-mated rats were exposed to nitrofen or vehicle on gestational day 9 (D9). Fetal diaphragms (n= 72) and lungs (n= 48) were microdissected on D13, D15, and D18, and were divided into control and nitrofen-exposed specimens. Diaphragmatic and pulmonary gene expression levels ofPbx1, Meis1,andRunx1were analyzed by quantitative real-time polymerase chain reaction. Immunofluorescence-double-staining forPbx1,Meis1, andRunx1was combined with mesenchymal/myogenic markers Gata4 and myogenin to evaluate protein expression.ResultsRelative mRNA expression ofPbx1, Meis1,andRunx1was significantly decreased in PPFs (D13), developing diaphragms/lungs (D15), and muscularized diaphragms/differentiated lungs (D18) of nitrofen-exposed fetuses compared with controls. Confocal-laser-scanning-microscopy revealed markedly diminishedPbx1,Meis1, andRunx1immunofluorescence in diaphragmatic and pulmonary mesenchyme, associated with less proliferating mesenchymal cells in nitrofen-exposed fetuses on D13, D15, and D18 compared with controls.ConclusionDecreasedPbx1,Meis1, andRunx1expression during diaphragmatic development and lung branching morphogenesis may reduce mesenchymal cell proliferation, causing malformed PPFs and disrupted airway branching, thus leading to diaphragmatic defects and PH in the nitrofen-induced CDH model.
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DOI：
10.1002/bdra.20613
发表时间：
2010-01-01
影响因子：
--
作者：
Clugston, Robin D.;Zhang, Wei;Greer, John J.
通讯作者：
Greer, John J.
影响因子：
11.8
作者：
Vitobello, Antonio;Ferretti, Elisabetta;Lampe, Xavier;Vilain, Nathalie;Ducret, Sebastien;Ori, Michela;Spetz, Jean-Francois;Selleri, Licia;Rijli, Filippo M.
通讯作者：
Rijli, Filippo M.
除草醚诱导的先天性膈疝膈肌中 GATA4 表达降低。
DOI：
--
发表时间：
2013
期刊：
Birth defects research. Part B. Developmental and reproductice toxicology
影响因子：
--
作者：
J. Dingemann;T. Doi;J. Gosemann;E. Ruttenstock;Nana Nakazawa;P. Puri
通讯作者：
P. Puri
先天性膈疝致畸剂除草醚的作用机制。
DOI：
--
发表时间：
2007
期刊：
American Journal of Physiology - Lung cellular and Molecular Physiology
影响因子：
--
作者：
B. R. Noble;Randal P. Babiuk;Robin D. Clugston;T. Underhill;Hui;R. Kawaguchi;P. Walfish;R. Blomhoff;T. Gundersen;J. Greer
通讯作者：
J. Greer
影响因子：
2.4
作者：
Montedonico, Sandra;Sugimoto, Kaoru;Puri, Prem
通讯作者：
Puri, Prem