Alejandre-Alcázar Miguel A, Michiels-Corsten Matthias, Vicencio Alfin G, Reiss Irwin, Ryu Julie, de Krijger Ronald R, Haddad Gabriel G, Tibboel Dick, Seeger Werner, Eickelberg Oliver, Morty Rory E
Department of Internal Medicine, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany.
Dev Dyn. 2008 Jan;237(1):259-69. doi: 10.1002/dvdy.21403.
Although transforming growth factor-beta (TGF-beta) signaling negatively regulates branching morphogenesis in early lung development, few studies to date have addressed the role of this family of growth factors during late lung development. We describe here that the expression, tissue localization, and activity of components of the TGF-beta signaling machinery are dynamically regulated during late lung development in the mouse and human. Pronounced changes in the expression and localization of the TGF-beta receptors Acvrl1, Tgfbr1, Tgfbr2, Tgfbr3, and endoglin, and the intracellular messengers Smad2, Smad3, Smad4, Smad6, and Smad7 were noted as mouse and human lungs progressed through the canalicular, saccular, and alveolar stages of development. TGF-beta signaling, assessed by phosphorylation of Smad2, was detected in the vascular and airway smooth muscle, as well as the alveolar and airway epithelium throughout late lung development. These data suggest that active TGF-beta signaling is required for normal late lung development.
尽管转化生长因子-β（TGF-β）信号通路在肺早期发育中对分支形态发生起负调控作用，但迄今为止，很少有研究探讨该生长因子家族在肺晚期发育中的作用。我们在此描述，在小鼠和人类肺晚期发育过程中，TGF-β信号传导机制各组分的表达、组织定位及活性受到动态调控。随着小鼠和人类肺脏经历小管期、囊状期和肺泡期的发育，TGF-β受体Acvrl1、Tgfbr1、Tgfbr2、Tgfbr3和内皮糖蛋白，以及细胞内信使分子Smad2、Smad3、Smad4、Smad6和Smad7的表达和定位出现显著变化。通过Smad2磷酸化评估的TGF-β信号传导，在整个肺晚期发育过程中的血管和气道平滑肌以及肺泡和气道上皮中均有检测到。这些数据表明，活跃的TGF-β信号传导是肺正常晚期发育所必需的。
