| First Author | Zeng X | Year | 2001 |
| Journal | Dev Dyn | Volume | 221 |
| Issue | 3 | Pages | 289-301 |
| PubMed ID | 11458389 | Mgi Jnum | J:70281 |
| Mgi Id | MGI:2136714 | Doi | 10.1002/dvdy.1140 |
| Citation | Zeng X, et al. (2001) TGF-beta1 perturbs vascular development and inhibits epithelial differentiation in fetal lung in vivo. Dev Dyn 221(3):289-301 |
| abstractText | Members of the transforming growth factor beta (TGF-beta) family of polypeptides have been implicated in morphogenesis and differentiation in numerous tissues, including the lung. In order to further define effects of TGF-beta signaling in lung morphogenesis, a constitutively active form of TGF-beta1 was expressed in respiratory epithelial cells of the fetal mouse lung in vivo. Expression of TGF-beta1 arrested lung morphogenesis in the pseudoglandular stage of development, inhibiting synthesis of differentiation-dependent proteins, SP-B, SP-C, and CCSP, and maintaining embryonic patterns of staining for thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor-3beta (HNF-3beta). The pulmonary mesenchyme was thickened and vascular density was increased by TGF-beta1. TGF-beta1 decreased expression of vascular endothelial growth factor-A (VEGF-A) mRNA and protein, and the abundance of Flk-1 mRNA in the lung mesenchyme. Distribution of platelet-endothelial cell adhesion molecule (PECAM)-1, a marker of pulmonary blood vessels, was altered, and ultrastructural studies demonstrated that TGF-beta1 inhibited vascular development in the fetal lung. TGF-beta1 perturbed both epithelial cell differentiation and formation of the pulmonary vasculature, supporting the concept that precise control of signaling via the TGF-beta receptor pathway is critical for normal lung morphogenesis. Copyright 2001 Wiley-Liss, Inc. |
