| First Author | Miao Q | Year | 2021 |
| Journal | Am J Physiol Lung Cell Mol Physiol | PubMed ID | 33881909 |
| Mgi Jnum | J:304787 | Mgi Id | MGI:6695026 |
| Doi | 10.1152/ajplung.00299.2020 | Citation | Miao Q, et al. (2021) Abrogation of mesenchyme-specific TGF-beta signaling results in lung malformation with prenatal pulmonary cysts in mice. Am J Physiol Lung Cell Mol Physiol |
| abstractText | The TGF-beta signaling pathway plays a pivotal role in controlling organogenesis during fetal development. Although the role of TGF-beta signaling in promoting lung alveolar epithelial growth has been determined, mesenchymal TGF-beta signaling in regulating lung development has not been studied in vivo due to a lack of genetic tools for specifically manipulating gene expression in lung mesenchymal cells. Therefore, the integral roles of TGF-beta signaling in regulating lung development and congenital lung diseases are not completely understood. Using a Tbx4 lung enhancer-driven Tet-On inducible Cre transgenic mouse system, we have developed a mouse model in which lung mesenchyme-specific deletion of TGF-beta receptor 2 gene (Tgfbr2) is achieved. Reduced airway branching accompanied by defective airway smooth muscle growth and later peripheral cystic lesions occurred when lung mesenchymal Tgfbr2 was deleted from embryonic day 13.5 to 15.5, resulting in postnatal death due to respiratory insufficiency. Although cell proliferation in both lung epithelium and mesenchyme was reduced, epithelial differentiation was not significantly affected. Tgfbr2 downstream Smad-independent ERK1/2 may mediate these mesenchymal effects of TGF-beta signaling through the GSK3beta--beta-catenin--Wnt canonical pathway in fetal mouse lung. Our study suggests that Tgfbr2-mediated TGF-beta signaling in prenatal lung mesenchyme is essential for lung development and maturation, and defective TGF-beta signaling in lung mesenchyme may be related to abnormal airway branching morphogenesis and congenital airway cystic lesions. |
