Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti-CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs. Differentiation of FoxD1-progenitor derived pericytes into myofibroblasts involves CCN2 expression and contributes importantly to maladaptive tissue remodeling in for example kidney and lung fibrosis models. To generate a model for studying the contribution of CCN2 expression in FoxD1-progenitor derived cells to development of fibrotic tissue remodeling, we set out to establish a FoxD1Cre - CCN2flox/flox mouse colony. However, all double-transgenic mice died soon after birth due to asphyxia. Histopathological examination revealed a reduction in alveolar space and lung weight, and subtle axial (thoracic and cervical) skeletal deformities. Together with the previously reported association of a FoxD1 containing locus with human adolescent idiopathic scoliosis, our data suggest that the fatal pulmonary hypoplasia resulting from selective deletion of CCN2 from FoxD1-progenitor derived mesenchymal cells developed secondary to impaired breathing movements due to aberrant axial skeletogenesis.

中文翻译：

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更正为：FoxD1驱动的CCN2缺失导致轴向骨骼畸形，肺发育不全和新生儿窒息性死亡。

肺纤维化是一种严重致残的疾病，经常导致死亡。CCN2（细胞通讯网络因子2，也称为CTGF）是已知的纤维化介质，目前正在进行有关抗CCN2在肺纤维化中功效的临床试验。叉头箱D1（FoxD1）转录因子在几种间充质细胞类型中瞬时表达，包括胎儿肺中的那些。FoxD1祖细胞衍生的成周细胞分化为成肌纤维细胞涉及CCN2表达，并且在例如肾脏和肺纤维化模型中对适应不良的组织重塑起重要作用。为了生成一个模型来研究FoxD1祖细胞中CCN2表达对纤维化组织重塑发展的贡献，我们着手建立一个FoxD1Cre-CCN2flox / flox小鼠菌落。然而，所有双转基因小鼠出生后均因窒息死亡。组织病理学检查显示肺泡间隙和肺重量减少，以及细微的轴向（胸和颈）骨骼畸形。连同先前报道的含有FoxD1的基因座与人类青春期特发性脊柱侧弯的关联，我们的数据表明，由于异常的轴向骨骼生成导致呼吸运动受损，继发于FoxD1祖细胞衍生的间充质细胞中CCN2的选择性缺失导致了致命的肺发育不全。