Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Integrated Cardio Metabolic Centre, Karolinska Institute, SE-141 57 Huddinge, Sweden.
Development. 2018 Apr 10;145(7):dev161976. doi: 10.1242/dev.161976.
Platelet-derived growth factor A (PDGF-A) signaling through PDGF receptor α is essential for alveogenesis. Previous studies have shown that mouse lungs have enlarged alveolar airspace with absence of secondary septation, both distinctive features of bronchopulmonary dysplasia. To study how PDGF-A signaling is involved in alveogenesis, we generated lung-specific knockout mice () and characterized their phenotype postnatally. Histological differences between mutant mice and littermate controls were visible after the onset of alveogenesis and maintained until adulthood. Additionally, we generated mice in which cells exhibit nuclear GFP expression. In the absence of PDGF-A, the number of cells was significantly decreased. In addition, proliferation of cells was reduced. During alveogenesis, myofibroblasts failed to form the α-smooth muscle actin rings necessary for alveolar secondary septation. These results indicate that PDGF-A signaling is involved in myofibroblast proliferation and migration. In addition, we show an increase in both the number and proliferation of alveolar type II cells in lungs, suggesting that the increased alveolar airspace is not caused solely by deficient myofibroblast function.
血小板衍生生长因子 A (PDGF-A) 通过 PDGF 受体 α 的信号传导对于肺泡发生是必需的。先前的研究表明，小鼠肺具有扩大的肺泡气腔，没有次级间隔形成，这是支气管肺发育不良的两个显著特征。为了研究 PDGF-A 信号传导如何参与肺泡发生，我们生成了肺特异性敲除小鼠 () ，并在出生后对其表型进行了特征描述。在肺泡发生开始后，可以看到突变小鼠和同窝对照之间的组织学差异，并持续到成年。此外，我们生成了细胞中显示核 GFP 表达的 小鼠。在缺乏 PDGF-A 的情况下，细胞的数量显著减少。此外，细胞的增殖减少。在肺泡发生过程中，肌成纤维细胞未能形成肺泡次级间隔所必需的α-平滑肌肌动蛋白环。这些结果表明 PDGF-A 信号传导参与肌成纤维细胞的增殖和迁移。此外，我们显示 肺中的肺泡 II 型细胞数量和增殖均增加，表明增加的肺泡气腔不仅仅是由于肌成纤维细胞功能缺陷引起的。
